Developmental Stage-specific Gene Research Articles

Roles of Nuclear Orphan Receptors TR2 and TR4 during Hematopoiesis.

TR2 and TR4 (NR2C1 and NR2C2, respectively) are evolutionarily conserved nuclear orphan receptors capable of binding direct repeat sequences in a stage-specific manner. Like other nuclear receptors, TR2 and TR4 possess important roles in transcriptional activation or repression with developmental stage and tissue specificity. TR2 and TR4 bind DNA and possess the ability to complex with available cofactors mediating developmental stage-specific actions in primitive and definitive erythrocytes. In erythropoiesis, TR2 and TR4 are required for erythroid development, maturation, and key erythroid transcription factor regulation. TR2 and TR4 recruit and interact with transcriptional corepressors or coactivators to elicit developmental stage-specific gene regulation during hematopoiesis.

In silico analysis and expression profiling reveal the presence of abiotic stress and developmental stage specific Aconitase genes in rice (Oryza sativa L.)

The growth and yield of crops have been significantly affected by abiotic stresses. Although respiratory metabolism is integral to plants, its understanding within the context of stress adaptation remains limited . While the rice genome contains three Aconitase genes, their specific roles in abiotic stress tolerance and plant development remain largely unexplored. This study aimed to characterize the Aconitase gene family in rice, shedding light on the evolution of Aconitase and its involvement in diverse developmental processes, as well as its response under various abiotic stress conditions. Phylogenetic analysis indicated the evolutionary relationship between rice Aconitase genes and those of other plant species. The prediction of promoter cis-elements revealed the presence of diverse cis-acting elements associated with the response to abiotic stress within the Aconitase gene family. In addition, an analysis of public RNA-seq data indicated the potential involvement of Aconitase genes in various developmental processes and mechanisms related to stress tolerance. Further, qRT-PCR confirmed the expression patterns of Aconitase genes. Expression analysis revealed differential expression of Aconitase genes under cold, drought, ABA, and salt stresses. Elevated levels of the OsAco1 transcript resulted in a phenotype that exhibited increased tolerance to salt stress. Biochemical analysis revealed higher Aconitase activity in the overexpressed line compared to the control plant. Furthermore, the overexpressed line exhibited improved growth and lower H2O2 levels than the control plant following a 2-hour exposure to 200 mM salt stress. These findings suggest a potential role of Aconitase in enhancing salt stress tolerance. Moreover, they lay the foundation for further exploration into the precise involvement of Aconitase in plant developmental processes under various stress conditions, with the ultimate aim of developing salt-tolerant rice cultivars.

Histone H3.3 variant plays a critical role on zygote-to-oocyst development in malaria parasites

The Plasmodium life cycle involves differentiation into multiple morphologically distinct forms, a process regulated by developmental stage-specific gene expression. Histone proteins are involved in epigenetic regulation in eukaryotes, and the histone variant H3.3 plays a key role in the regulation of gene expression and maintenance of genomic integrity during embryonic development in mice. However, the function of H3.3 through multiple developmental stages in Plasmodium remains unknown. To examine the function of H3.3, h3.3-deficient mutants (Δh3.3) were generated in P. berghei. The deletion of h3.3 was not lethal in blood stage parasites, although it had a minor effect of the growth rate in blood stage; however, the in vitro ookinete conversion rate was significantly reduced, and the production of the degenerated form was increased. Regarding the mosquito stage development of Δh3.3, oocysts number was significantly reduced, and no sporozoite production was observed. The h3.3 gene complemented mutant have normal development in mosquito stage producing mature oocysts and salivary glands contained sporozoites, and interestingly, the majority of H3.3 protein was detected in female gametocytes. However, Δh3.3 male and female gametocyte production levels were comparable to the wild-type levels. Transcriptome analysis of Δh3.3 male and female gametocytes revealed the upregulation of several male-specific genes in female gametocytes, suggesting that H3.3 functions as a transcription repressor of male-specific genes to maintain sexual identity in female gametocytes. This study provides new insights into the molecular biology of histone variants H3.3 which plays a critical role on zygote-to-oocyst development in primitive unicellular eukaryotes.

Functional characterization of Cinnamate 4-hydroxylase gene family in soybean (Glycine max).

Cinnamate 4-hydroxylase (C4H) is the first key cytochrome P450 monooxygenase (P450) enzyme in the phenylpropanoid pathway. It belongs to the CYP73 family of P450 superfamily, and catalyzes the conversion of trans-cinnamic acid to p-coumaric acid. Since p-coumaric acid serves as the precursor for the synthesis of a wide variety of metabolites involved in plant development and stress resistance, alteration in the expression of soybean C4H genes is expected to affect the downstream metabolite levels, and its ability to respond to stress. In this study, we identified four C4H genes in the soybean genome that are distributed into both class I and class II CYP73 family. GmC4H2, GmC4H14 and GmC4H20 displayed tissue- and developmental stage-specific gene expression patterns with their transcript accumulation at the highest level in root tissues. GmC4H10 appears to be a pseudogene as its transcript was not detected in any soybean tissues. Furthermore, protein homology modelling revealed substrate docking only for GmC4H2, GmC4H14 and GmC4H20. To demonstrate the function of GmC4Hs, we modified a cloning vector for the heterologous expression of P450s in yeast, and used it for microsomal protein production and enzyme assay. Our results confirmed that GmC4H2, GmC4H14 and GmC4H20 contain the ability to hydroxylate trans-cinnamic acid with varying efficiencies.

Developmental Transcriptome Analysis of Red-Spotted Apollo Butterfly, Parnassius bremeri.

Parnassius bremeri (P. bremeri), a member of the genus Snow Apollo in the swallowtail family (Papilionidae), is a high alpine butterfly that lives in Russia, Korea, and China. It is an endangered wildlife (Class I) in South Korea and is a globally endangered species. The lack of transcriptomic and genomic resources of P. bremeri significantly hinders the study of its population genetics and conservation. The detailed information of the developmental stage-specific gene expression patterns of P. bremeri is of great demand for its conservation. However, the molecular mechanism underlying the metamorphic development of P. bremeri is still unknown. In the present study, the differentially expressed genes (DEGs) across the metamorphic developmental stages were compared using high-throughput transcriptome sequencing. We identified a total of 72,161 DEGs from eight comparisons. GO enrichment analysis showed that a range of DEGs were responsible for cuticle development and the melanin biosynthetic pathway during larval development. Pathway analysis suggested that the signaling pathways, such as the Wnt signaling pathway, hedgehog signaling pathway and Notch signaling pathway, are regulated during the developmental stages of P. bremeri. Furthermore, sensory receptors were also activated, especially during the larval to adult transition stage. Collectively, the results of this study provide a preliminary foundation and understanding of the molecular mechanism in their transcriptomes for further research on the metamorphic development of P. bremeri.

Capturing Protein-Nucleic Acid Interactions by High-Intensity Laser-Induced Covalent Cross-Linking†.

Interactions of DNA with structural proteins such as histones, regulatory proteins and enzymes play a crucial role in major cellular processes such as transcription, replication and repair. The invivo mapping and characterization of the binding sites of the involved biomolecules are of primary importance for a better understanding of genomic deployment that is implicated in tissue and developmental stage-specific gene expression regulation. The most powerful and commonly used approach to date is immunoprecipitation of chemically cross-linked chromatin (XChIP) coupled with sequencing analysis (ChIP-seq). While the resolution and the sensitivity of the high-throughput sequencing techniques have been constantly improved, little progress has been achieved in the cross-linking step. Because of its low efficiency, the use of the conventional UVC lamps remains very limited while the formaldehyde method was established as the "gold standard" cross-linking agent. Efficient biphotonic cross-linking of directly interacting nucleic acid-protein complexes by a single short UV laser pulse has been introduced as an innovative technique for overcoming limitations of conventionally used chemical and photochemical approaches. In this survey, the main available methods including the laser approach are critically reviewed for their ability to generate DNA-protein cross-links invitro model systems and cells.

M6A Topological Transition Coupled to Developmental Regulation of Gene Expression During Mammalian Tissue Development.

N6-methyladenosine (m6A) is the most prevalent internal modification and reversible epitranscriptomic mark in messenger RNAs (mRNAs) and plays essential roles in a variety of biological processes. However, the dynamic distribution patterns of m6A and their significance during mammalian tissue development are poorly understood. Here, we found that based on m6A distribution patterns, protein-coding genes were classified into five groups with significantly distinct biological features and functions. Strikingly, comparison of the m6A methylomes of multiple mammalian tissues between fetal and adult stages revealed dynamic m6A topological transition during mammalian tissue development, and identified large numbers of genes with significant m6A loss in 5′UTRs or m6A gain around stop codons. The genes with m6A loss in 5′UTRs were highly enriched in developmental stage-specific genes, and their m6A topological transitions were strongly associated with gene expression regulation during tissue development. The genes with m6A gain around the stop codons were associated with tissue-specific functions. Our findings revealed the existence of different m6A topologies among protein-coding genes that were associated with distinct characteristics. More importantly, these genes with m6A topological transitions were crucial for tissue development via regulation of gene expression, suggesting the importance of dynamic m6A topological transitions during mammalian tissue development.

Comparative Transcriptome Analysis Reveals Common and Developmental Stage-Specific Genes That Respond to Low Nitrogen in Maize Leaves.

A growing leaf can be divided into three sections: division zone, elongation zone, and maturation zone. In previous studies, low nitrogen (LN) inhibited maize growth and development, especially leaf growth; however, the gene expression in response to LN in different regions in leaf were not clear. Here, using hydroponics and a transcriptome approach, we systematically analyzed the molecular responses of those zones and differentially expressed genes (DEG) in response to LN supply. Developmental stage-specific genes (SGs) were highly stage-specific and involved in distinct biological processes. SGs from division (SGs–DZ) and elongation zones (SGs–EZ) were more related to developmentally dependent processes, whereas SGs of the maturation zone (SGs–MZ) were more related to metabolic processes. The common genes (CGs) were overrepresented in carbon and N metabolism, suggesting that rebalancing carbon and N metabolism in maize leaves under LN condition was independent of developmental stage. Coexpression modules (CMs) were also constructed in our experiment and a total of eight CMs were detected. Most of SGs–DZ and SGs–EZ were classified into a set termed CM turquoise, which was mainly enriched in ribosome and DNA replication, whereas several genes from SGs–MZ and CGs were clustered into CM blue, which mainly focused on photosynthesis and carbon metabolism. Finally, a comprehensive coexpression network was extracted from CM blue, and several maize CONSTANS-LIKE(ZmCOL) genes seemed to participate in regulating photosynthesis in maize leaves under LN condition in a developmental stage-specific manner. With this study, we uncovered the LN-responsive CGs and SGs that are important for promoting plant growth and development under insufficient nitrogen supply.

Selection and evaluation of RT-qPCR reference genes for expression analysis in the tiny egg parasitoid wasp, Trichogramma dendrolimi matsumura (Hymenoptera: Trichogrammatidae)

• This study identified reference genes for RT-qPCR analysis of T. dendrolimi. • This study confirmed appropriate combination of reference genes under different factors. • The best-suited reference genes can differ in response to diverse factors. • Robust procedures were established to quantify gene expression in T. dendrolimi. The egg parasitoid, Trichogramma spp., is an important biological control agent used against a broad range of Lepidopteran pests in agriculture and forestry. The biology of Trichogramma has been studied in details. Further studies should focus on the molecular mechanisms of Trichogramma by qualifying the expression of related genes It is critical to select appropriate reference genes for normalizing RT-qPCR results and establishing a robust method for quantifying target gene expression. This study aimed to identify and validate appropriate reference genes for use in RT-qPCR analysis of Trichogramma dendrolimi . Ten candidate housekeeping genes, namely beta-actin ( ACTIN ), forkhead box O ( FOXO ), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), heat shock protein 90 ( HSP90 ), ribosomal protein L10a ( RPL10a ), L18 ( RPL18 ), L28 ( RPL28 ), S13 ( RPS13 ), S15 ( RPS15 ), and superoxide dismutase ( SOD ), were tested for their suitability as reference genes for developmental stage (3rd, 4th, 5th, 6th, 7th, 8th, 9th, and 10th day after parasitization), tissue (head, thorax, and abdomen of adults), sex of adults (male and female), and temperature (17℃, 25℃, and 32℃). According to the GeNorm analysis, a robust analysis should involve using an appropriate combination of reference genes, namely, at least three genes for different development stages, two genes for different tissues, two genes for different sex, and two genes for different temperatures, respectively. According to the RelFinder method by the integrated results of GeNorm, NormFinder, BestKeeper, and the ΔCt method, we identified the developmental stage-specific reference genes SOD , GAPDH , and ACTIN ; tissue-specific reference genes RPL18 and RPS15 ; sex-specific reference genes RPL18 and SOD ; and temperature-specific reference genes RPL18 and RPL10a . This study provides a standardized procedure for the quantification of gene expression in T. dendrolimi and will be helpful for future biological control programs using Trichogramma wasps.

In heart failure reactivation of RNA-binding proteins is associated with the expression of 1,523 fetal-specific isoforms.

Reactivation of fetal-specific genes and isoforms occurs during heart failure. However, the underlying molecular mechanisms and the extent to which the fetal program switch occurs remains unclear. Limitations hindering transcriptome-wide analyses of alternative splicing differences (i.e. isoform switching) in cardiovascular system (CVS) tissues between fetal, healthy adult and heart failure have included both cellular heterogeneity across bulk RNA-seq samples and limited availability of fetal tissue for research. To overcome these limitations, we have deconvoluted the cellular compositions of 996 RNA-seq samples representing heart failure, healthy adult (heart and arteria), and fetal-like (iPSC-derived cardiovascular progenitor cells) CVS tissues. Comparison of the expression profiles revealed that reactivation of fetal-specific RNA-binding proteins (RBPs), and the accompanied re-expression of 1,523 fetal-specific isoforms, contribute to the transcriptome differences between heart failure and healthy adult heart. Of note, isoforms for 20 different RBPs were among those that reverted in heart failure to the fetal-like expression pattern. We determined that, compared with adult-specific isoforms, fetal-specific isoforms encode proteins that tend to have more functions, are more likely to harbor RBP binding sites, have canonical sequences at their splice sites, and contain typical upstream polypyrimidine tracts. Our study suggests that compared with healthy adult, fetal cardiac tissue requires stricter transcriptional regulation, and that during heart failure reversion to this stricter transcriptional regulation occurs. Furthermore, we provide a resource of cardiac developmental stage-specific and heart failure-associated genes and isoforms, which are largely unexplored and can be exploited to investigate novel therapeutics for heart failure.

Single-cell transcriptomics reveals hidden information in trypanosomatids

Dixenic parasites often encounter environmental extremes during the transition from vector to host. Preadapted transmission stages overcome these challenges to promote parasites' survival and ensure life cycle progression. Recently, Vigneron et al. and Briggs et al. used single-cell transcriptomics to investigate developmental stage specific gene expression patterns during parasite differentiation.

Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration

Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote regeneration of RGC axons, we identified transcription factors (TF) and open chromatin regions that are enriched in rat embryonic RGCs (high axon growth capacity) compared to postnatal RGCs (low axon growth capacity). We found that developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the regions of the chromatin that were more accessible in embryonic RGCs. Proteomic analysis of purified rat RGC nuclei confirmed the expression of TFs with potential role in axon growth such as CREB, CTCF, YY1, and JUND. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon regeneration. Consistently, overexpression of CREB fused to the VP64 transactivation domain in mouse RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.

Choice of the Promoter for Tissue and Developmental Stage-Specific Gene Expression.

Transgenic technologies belong to important tools of reverse genetics and biotechnology in plants. Targeted genetic modifications can reveal functions of genes of interest, change metabolic and regulatory pathways, or result in accumulation of valuable proteins or metabolites. However, to be efficient in targeted genetic modification, the chimeric gene construct should be designed properly. In particular, the promoters used to control transgene expression need to be carefully chosen. Most promoters in widely used vectors belong to strong and constitutively expressed variants. However, in many cases transgene expression has to be restricted to certain tissue, stage of development, or response to some internal or external stimuli. In turn, a large variety of tissue-specific promoters have been studied and information on their characteristics may be recovered from the literature. An appropriate promoter may be selected and used in genetic construct to optimize the transgene transcription pattern. We have previously designed the TGP database (TransGene Promoters, http://wwwmgs.bionet.nsc.ru/mgs/dbases/tgp/home.html ) collecting information from the publications in this field. Here we review the wide range of noncanonical tissue-specific and developmentally regulated promoters that might be used for transgene expression control.

In-silico prediction of microRNA targets and finding genes suggesting significant involvement in the development of Glycine max seed

Glycine max is a worldwide leading economic crop and its seeds are deepening with proteins and oils which supply food and sustenance to all being. Various amounts of alimentary constituents are racked up in the G. max seed in the period of its ontogenesis. Thus, grasping the regulation of biological functions during seed enlargement belong to the basics for crop enhancement. The gene regulatory characteristics of miRNAs in G. max attracted us to focus on its target gene prediction, gene ontology (GO) analysis and expression pattern to their miRNA target genes, which suggest significant involvement in the development of G. max seed. Seven miRNAs have been found from the differential gene expression analysis of development stage 0–4 mm vs. 12–16 mm of G. max seed on the statistical parameter of p value ≤ 0.05 by computational-based microarray data analysis for miRNA target gene prediction. The miRNA target prediction analysis showed total 23 genes that were cleaved from 6 miRNAs, and computationally validated by identifying t-plots of miRNA targets using CleaveLand tool. GO results confirmed that the differentially expressed target genes could be classified into 20 molecular function categories, 73 biological process categories, and 10 cell components categories. On the basis of GO results, two genes were found to be significantly involved in the developmental process of G.max seed. The first miRNA target gene Glyma.01g119500 was predicted to annotate for embryo development ending in seed dormancy, seed dormancy, seed maturation, and seed germination. The second miRNA target gene Glyma.15g005300 was found to be involved in the regulation of seed germination. The Soybean eFP browser analysis suggests that the gene Glyma.01g119500 and Glyma.15g005300 reaches its maximum expression level of 35.88 and 26.6 respectively in the Soybean data source. The present study provides an avenue to explore more genomic and proteomic information about G. max seed developmental stage-specific miRNA target genes.

Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation.

The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage–specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type–specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell–progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.

Dynamic control of enhancer activity drives stage-specific gene expression during flower morphogenesis

Enhancers are critical for developmental stage-specific gene expression, but their dynamic regulation in plants remains poorly understood. Here we compare genome-wide localization of H3K27ac, chromatin accessibility and transcriptomic changes during flower development in Arabidopsis. H3K27ac prevalently marks promoter-proximal regions, suggesting that H3K27ac is not a hallmark for enhancers in Arabidopsis. We provide computational and experimental evidence to confirm that distal DNase І hypersensitive sites are predictive of enhancers. The predicted enhancers are highly stage-specific across flower development, significantly associated with SNPs for flowering-related phenotypes, and conserved across crucifer species. Through the integration of genome-wide transcription factor (TF) binding datasets, we find that floral master regulators and stage-specific TFs are largely enriched at developmentally dynamic enhancers. Finally, we show that enhancer clusters and intronic enhancers significantly associate with stage-specific gene regulation by floral master TFs. Our study provides insights into the functional flexibility of enhancers during plant development, as well as hints to annotate plant enhancers.

Genome-wide analysis of developmental stage-specific transcriptome in Bradysia odoriphaga

Bradysia odoriphaga is a serious pest of the Chinese chive; however, detailed information regarding the developmental stage-specific gene expression patterns of B. odoriphaga is not yet available. In this study, RNA sequencing (RNA-seq) was performed to determine the gene expression patterns of developmental stages including the eggs, second instar larvae, fourth instar larvae, pupae, and adults of B. odoriphaga. Analysis of 15 samples revealed an average of 89.56% of the clean reads could be mapped onto the assembled UniGene database. Cluster tree analysis showed that the expression patterns were stage-specific and that samples of the second and fourth instar larvae clustered in one group, while those of eggs, pupae, and adults clustered in another group. Differential expression unigenes (DEUs) for sequential developmental stages were between 3314 and 10,632. A total of 1910–7756 DEUs of sequential developmental stages were assigned into 45–56 gene ontology categories and 1165–3845 DEUs were mapped into Kyoto Encyclopedia of Genes and Genomes pathways. The expression of DEUs related to growth and development showed that hormone receptors highly expressed in the pupal stage, while chitinases were highly expressed in the larval stage. The results of quantitative real time polymerase chain reaction (qRT-PCR) and RNA-seq expression agreed well for 12 growth- and development-related unigenes. This study identified DEUs for sequential developmental stages of B. odoriphaga. Gene Ontology classifications and KEGG pathway identification of DEUs not only provide information useful for understanding insect growth and development but also for exploring novel approaches to control B. odoriphaga.

Comprehensive Transcriptional Profiling of the Gastrointestinal Tract of Ruminants from Birth to Adulthood Reveals Strong Developmental Stage Specific Gene Expression.

One of the most significant physiological challenges to neonatal and juvenile ruminants is the development and establishment of the rumen. Using a subset of RNA-Seq data from our high-resolution atlas of gene expression in sheep (Ovis aries) we have provided the first comprehensive characterization of transcription of the entire gastrointestinal (GI) tract during the transition from pre-ruminant to ruminant. The dataset comprises 164 tissue samples from sheep at four different time points (birth, one week, 8 weeks and adult). Using network cluster analysis we illustrate how the complexity of the GI tract is reflected in tissue- and developmental stage-specific differences in gene expression. The most significant transcriptional differences between neonatal and adult sheep were observed in the rumen complex. Comparative analysis of gene expression in three GI tract tissues from age-matched sheep and goats revealed species-specific differences in genes involved in immunity and metabolism. This study improves our understanding of the transcriptomic mechanisms involved in the transition from pre-ruminant to ruminant by identifying key genes involved in immunity, microbe recognition and metabolism. The results form a basis for future studies linking gene expression with microbial colonization of the developing GI tract and provide a foundation to improve ruminant efficiency and productivity through identifying potential targets for novel therapeutics and gene editing.

Frequent monoallelic or skewed expression for developmental genes in CNS-derived cells and evidence for balancing selection

Cellular mosaicism due to monoallelic autosomal expression (MAE), with cell selection during development, is becoming increasingly recognized as prevalent in mammals, leading to interest in understanding its extent and mechanism(s). We report here use of clonal cell lines derived from the CNS of adult female [Formula: see text] hybrid (C57BL/6 X JF1) mice to characterize MAE as neural stem cells (nscs) differentiate to astrocyte-like cells (asls). We found that different subsets of genes show MAE in the two populations of cells; in each case, there is strong enrichment for genes specific to the respective developmental state. Genes that exhibit MAE are 22% of nsc-specific genes and 26% of asl-specific genes. Moreover, the promoters of genes with MAE have reduced CpG dinucleotides but increased CpG differences between the two parental mouse strains. Extending the study of variability to wild populations of mice, we found evidence for balancing selection as a contributing force in evolution of those genes showing developmental specificity (i.e., expressed in either nsc or asl), not just for genes showing MAE. Furthermore, we found that genes showing skewed allelic expression (SKE) were similarly enriched among cell type-specific genes and also showed a heightened probability of balancing selection. Thus, developmental stage-specific genes and genes with MAE or SKE seem to make up overlapping classes subject to selection for increased diversity. The implications of these results for development and evolution are discussed in the context of a model with stochastic epigenetic modifications taking place only during a relatively brief developmental window.

Atlas of tissue- and developmental stage specific gene expression for the bovine insulin-like growth factor (IGF) system.

The insulin-like growth factor (IGF) axis is fundamental for mammalian growth and development. However, no comprehensive reference data on gene expression across tissues and pre- and postnatal developmental stages are available for any given species. Here we provide systematic promoter- and splice variant specific information on expression of IGF system components in embryonic (Day 48), fetal (Day 153), term (Day 277, placenta) and juvenile (Day 365–396) tissues of domestic cow, a major agricultural species and biomedical model. Analysis of spatiotemporal changes in expression of IGF1, IGF2, IGF1R, IGF2R, IGFBP1-8 and IR genes, as well as lncRNAs H19 and AIRN, by qPCR, indicated an overall increase in expression from embryo to fetal stage, and decrease in expression from fetal to juvenile stage. The stronger decrease in expression of lncRNAs (average ―16-fold) and ligands (average ―12.1-fold) compared to receptors (average ―5.7-fold) and binding proteins (average ―4.3-fold) is consistent with known functions of IGF peptides and supports important roles of lncRNAs in prenatal development. Pronounced overall reduction in postnatal expression of IGF system components in lung (―12.9-fold) and kidney (―13.2-fold) are signatures of major changes in organ function while more similar hepatic expression levels (―2.2-fold) are evidence of the endocrine rather than autocrine/paracrine role of IGFs in postnatal growth regulation. Despite its rapid growth, placenta displayed a more stable expression pattern than other organs during prenatal development. Quantitative analyses of contributions of promoters P0-P4 to global IGF2 transcript in fetal tissues revealed that P4 accounted for the bulk of transcript in all tissues but skeletal muscle. Demonstration of IGF2 expression in fetal muscle and postnatal liver from a promoter orthologous to mouse and human promoter P0 provides further evidence for an evolutionary and developmental shift from placenta-specific P0-expression in rodents and suggests that some aspects of bovine IGF expression may be closer to human than mouse.