Domain-containing Gene Family Research Articles

Genome-wide identification and expression analysis of the SET domain-containing gene family in potato (Solanum tuberosum L.)

Genes containing the SET domain can catalyse histone lysine methylation, which in turn has the potential to cause changes to chromatin structure and regulation of the transcription of genes involved in diverse physiological and developmental processes. However, the functions of SET domain-containing (StSET) genes in potato still need to be studied. The objectives of our study can be summarized as in silico analysis to (i) identify StSET genes in the potato genome, (ii) systematically analyse gene structure, chromosomal distribution, gene duplication events, promoter sequences, and protein domains, (iii) perform phylogenetic analyses, (iv) compare the SET domain-containing genes of potato with other plant species with respect to protein domains and orthologous relationships, (v) analyse tissue-specific expression, and (vi) study the expression of StSET genes in response to drought and heat stresses. In this study, we identified 57 StSET genes in the potato genome, and the genes were physically mapped onto eleven chromosomes. The phylogenetic analysis grouped these StSET genes into six clades. We found that tandem duplication through sub-functionalisation has contributed only marginally to the expansion of the StSET gene family. The protein domain TDBD (PFAM ID: PF16135) was detected in StSET genes of potato while it was absent in all other previously studied species. This study described three pollen-specific StSET genes in the potato genome. Expression analysis of four StSET genes under heat and drought in three potato clones revealed that these genes might have non-overlapping roles under different abiotic stress conditions and durations. The present study provides a comprehensive analysis of StSET genes in potatoes, and it serves as a basis for further functional characterisation of StSET genes towards understanding their underpinning biological mechanisms in conferring stress tolerance.

Genome-Wide Identification, Structural Diversity Analysis and Expression Profiling of NBARC Domain-Containing Gene Family in Pisum sativum

Genome-Wide Identification, Structural Diversity Analysis and Expression Profiling of NBARC Domain-Containing Gene Family in Pisum sativum

Evolution and Expression of the Meprin and TRAF Homology Domain-Containing Gene Family in Solanaceae.

Meprin and TRAF homology (MATH)-domain-containing proteins are pivotal in modulating plant development and environmental stress responses. To date, members of the MATH gene family have been identified only in a few plant species, including Arabidopsis thaliana, Brassica rapa, maize, and rice, and the functions of this gene family in other economically important crops, especially the Solanaceae family, remain unclear. The present study identified and analyzed 58 MATH genes from three Solanaceae species, including tomato (Solanum lycopersicum), potato (Solanum tuberosum), and pepper (Capsicum annuum). Phylogenetic analysis and domain organization classified these MATH genes into four groups, consistent with those based on motif organization and gene structure. Synteny analysis found that segmental and tandem duplication might have contributed to MATH gene expansion in the tomato and the potato, respectively. Collinearity analysis revealed high conservation among Solanaceae MATH genes. Further cis-regulatory element prediction and gene expression analysis showed that Solanaceae MATH genes play essential roles during development and stress response. These findings provide a theoretical basis for other functional studies on Solanaceae MATH genes.

Identificação de todo o genoma e análise da expressão da família de genes contendo o domínio JmjC relacionada ao estresse abiótico e tratamentos fotoperiódicos em feijão mungo (Vigna radiataL.)

ABSTRACT: Although the JmjC domain-containing histone demethylases displayed a crucial role in maintaining the homeostasis of histone methylation, while the systematic identification and functional researches of JmjC domain-containing gene family have not been conducted in Mung bean (VrJMJgenes). According to the structural characteristics and phylogenetic relationship with their orthologs from Glycine max, Lotus japonicus, Medicagotruncatula, Arabidopsis thaliana, and Oryza sativa, a total of 18 VrJMJgenes were identified and divided into four clades (KDM3, KDM5. PKDM8, and PKDM9). Interspecies co-collinearity analysis showed the significant JmjC gene duplication events which have occurred during the Papilionoideae evolution. The exon/intron and domain organization of VrJMJgenes from the same clade (or subclade) were similar. All VrJMJ proteins contained a conserved JmjC domain, meanwhile other essential domains also have been found in some specific VrJMJ proteins which responsible for their functions. Numerous abiotic stress and light response related cis-elements associating with transcriptional regulation that were demonstrated in the promoter regions of VrJMJgenes(Pro VrJMJs ). Expression profiles of VrJMJgenes in different tissues showed that most genes displayed a tissue-specific expression in roots or leaves. The acronym RT-qPCR results showed that all VrJMJ genes displayed different degrees of abiotic stress (drought, salinity, and cold) and photoperiodic responses. Furthermore, VrJMJ3 and VrJMJ9 were significantly up-regulated after all three abiotic stress treatments, and VrJMJ13 exhibited a potential function in the photoperiodic regulation of Mung bean flowering. These results provided a clear understanding of VrJMJ genes, and laid a theoretical basis for further verification of their potential biological functions of VrJMJ genes.

Genome-wide analysis of DUF221 domain-containing gene family in common bean and identification of its role on abiotic and phytohormone stress response

Genome-wide analysis of DUF221 domain-containing gene family in common bean and identification of its role on abiotic and phytohormone stress response

Genome-wide identification, classification and expression analysis of the JmjC domain-containing histone demethylase gene family in Jatropha curcas L.

JmjC domain-containing proteins, an important family of histone lysine demethylase, play significant roles in maintaining the homeostasis of histone methylation. In this study, we comprehensively analyzed the JmjC domain-containing gene family in Jatropha curcas and found 20 JmjC domain-containing genes (JcJMJ genes). Phylogenetic analysis revealed that these JcJMJ genes can be classified into five major subgroups, and genes in each subgroup had similar motif and domain composition. Cis-regulatory element analysis showed that the number and types of cis-regulatory elements owned by the promoter of JcJMJ genes in different subgroup were significantly different. Moreover, miRNA target prediction result revealed a complicated miRNA-mediated post-transcriptional regulatory network, in which JcJMJ genes were regulated by different numbers and types of miRNAs. Further analysis of the tissue and stress expression profiles showed that many JcJMJ genes had tissue and stress expression specificity. All these results provided valuable information for understanding the evolution of JcJMJ genes and the complex transcriptional and post transcriptional regulation involved, and laid the foundation for further functional analysis of JcJMJ genes.

FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53.

BackgroundFork head domain-containing gene family (Fox) transcription factors, consisting of over 20 members, are involved in the progression of certain types of tumor. However, whether FOXN4 is involved in carcinogenesis and tumor progression is still unclear.PurposeIn this study, we investigated the clinicopathological significance and the underlying mechanism of FOXN4 in breast cancer.Methods and resultsWe examined the lower expression of FOXN4 in breast cancer tissues and cancer cell lines. The expression of FOXN4 is negatively correlated with tumor size and lymph node metastasis. Using CCK-8 assay, colony formation assay, wound healing assay, and Transwell assay, we revealed that FOXN4 notably decreased breast cancer cell proliferation, epithelial-mesenchymal transition and invasion in vitro. In addition, quantitative chromatin immunoprecipitation and luciferase assays determined that FOXN4 was able to directly bind with the promoter of P53. RT-qPCR and Western blotting analysis showed that FOXN4 could directly activate P53 expression. Functionally, P53 knockdown rescued the tumor inhibition effects of FOXN4 in breast cancer cells.ConclusionThe present study provides new insights into the role of FOXN4 in breast cancer progression and suggests FOXN4 might represent a potential therapeutic target in breast cancer by modulating P53.

POPDC proteins and cardiac function.

The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein-protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

P.143 - POPDC1 gene mutation screening in patients with LGMD and heart disturbances: a mutation load effect?

POPDC1 is the best-studied member of the Popeye domain-containing gene family. The members of this family encode transmembrane proteins, which are abundantly expressed in cardiac and skeletal muscle. The evolutionary conserved Popeye domain functions as a high-affinity 3'-5'-cyclic adenosine monophosphate (cAMP) binding domain. Recently, we identified recessive POPDC1 mutations in a family affected by Limb-girdle Muscular Dystrophy and atrioventricular (AV) block (OMIM LGMD2X). In order to evaluate if POPDC1 may contribute to phenotype variability in other LGMDs with or without cardiac involvement we screened by Sanger sequencing 166 patients with different phenotypes either orphan of gene mutations or with known gene mutations. We identified 8 different heterozygous POPDC1 mutations in 10 patients, 6 of them do also carry LMNA mutations, and 2 patients do carry Dysferlin mutations. Phenotypes vary from classical LGMD phenotype to pure cardiomyopathy with rhythm disturbances. It is emerging that the mutation load (occurrence of multiple mutations in different causative genes) plays a relevant role in phenotype modulation. We suggest that POPDC1 gene variations may contribute to the high clinical heterogeneity and intra- and interfamilial phenotypic variability of LMNA diseases. This hypothesis is supported by the known functional interaction between POPDC1 and LMNA.

Genome-wide analysis of DUF221 domain-containing gene family in Oryza species and identification of its salinity stress-responsive members in rice.

DUF221 domain-containing genes (DDP genes) play important roles in developmental biology, hormone signalling transduction, and responses to abiotic stress. Therefore to understand their structural and evolutionary relationship, we did a genome-wide analysis of this important gene family in rice. Further, through comparative genomics, DDP genes from Oryza sativa subsp. (indica), nine different wild species of rice and Arabidopsis were also identified. We also found an expansion of the DDP gene families in rice and Arabidopsis which is due to the segmental duplication events in some of the gene family members. In general, a highly purifying selection was found acting on all the deduced paralogous and orthologous DDP gene pairs. The data from microarray and subsequent qRT-PCR analysis revealed that although several OsDDPs were differentially regulated under salinity stress, yet OsDDP6 was upregulated at all the developmental stages in salt tolerant rice genotype, FL478. Interestingly, OsDDP6 was found to be involved in proline metabolism pathway as indicated by protein network analysis. The diverse gene structures, varied transmembrane topologies and the differential expression patterns implied the functional diversity in DDP genes. Therefore, the comprehensive evolutionary analysis of DDP genes from different Oryza species and Arabidopsis performed in this study will provide the basis for further functional validation studies vis-à-vis DDP genes of rice and other plant species.

Study of Genetic Association With DCDC2 and Developmental Dyslexia in Hong Kong Chinese Children.

Background:Doublecortin domain-containing 2 (DCDC2) is a doublecortin domain-containing gene family member and the doublecortin domain has been demonstrated to bind to tubulin and enhance microtubule polymerization. It has been associated with developmental dyslexia and this protein family member is thought to function in neuronal migration where it may affect the signaling of primary cilia.Objectives:The objective of the study is to find out if there is any association of genetic variants of DCDC2 with developmental dyslexia in Chinese children from Hong Kong.Methods:The dyslexic children were diagnosed as developmental dyslexia (DD) using the Hong Kong Test of Specific Learning Difficulties in Reading and Writing (HKT-SpLD) by the Department of Health, Hong Kong. Saliva specimens were collected and their genotypes of DCDC2 were studied by DNA sequencing or TaqMan Real Time PCR Assays.Results:The most significant marker is rs6940827 which is associated with DD with nominal p-value (0.011). However, this marker did not remain significant after multiple testing corrections and the adjusted p-value from permutation test was 0.1329. Using sliding window haplotype analysis, several haplotypes were found to be nominally associated with DD. The smallest nominal p values was 0.0036 (rs2996452-rs1318700, C-A). However, none of the p values could withstand the multiple testing corrections.Conclusion:Despite early findings that DCDC2 is a strong candidate for developmental dyslexia and that some of the genetic variants have been linked to brain structure and functions, our findings showed that DCDC2 is not strongly associated with dyslexia.

Systematic investigation of CMTM family genes suggests relevance to glioblastoma pathogenesis and CMTM1 and CMTM3 as priority targets.

The novel CKLF-like Marvel Transmembrane Domain-containing gene family (CMTM) consists of 8 members (CMTM1-8). As little is known about the oncogenic impact of these genes, we aimed to systematically investigate the relevance of CMTMs to glioblastoma pathogenesis. We performed mRNA expression analyses and survival correlations in glioblastoma patients. Moreover, we analyzed the impact of RNAi-based silencing and overexpression of CMTM family genes on tumor cell proliferation and invasion in vitro. CMTMs appeared to be widely regulated in the group of glioblastomas relative to non-neoplastic brain (NB) tissue (significant upregulation for CMTM2, 3, and 6 and significant downregulation for CMTM 4 and 8). For CMTM1, 5 and 7, we found aberrant expression levels in individual tumors. Functionally, CMTM1, 3, and 7 promoted tumor cell invasion, while CMTM1 additionally enhanced cell proliferation. In a large clinically annotated dataset, higher CMTM1 and 3 expression was significantly correlated with shorter overall survival. Our data thus suggest CMTM1 and 3 as priority targets in glioblastomas. Using a human phosphokinase protein expression profiling assay, we can provide first insights into signalling of these two genes that might be conveyed by growth factor receptor, Src family kinase and WNT activation.

AtRD22 and AtUSPL1, members of the plant-specific BURP domain family involved in Arabidopsis thaliana drought tolerance.

Crop plants are regularly challenged by a range of environmental stresses which typically retard their growth and ultimately compromise economic yield. The stress response involves the reprogramming of approximately 4% of the transcriptome. Here, the behavior of AtRD22 and AtUSPL1, both members of the Arabidopsis thaliana BURP (BNM2, USP, RD22 and polygalacturonase isozyme) domain-containing gene family, has been characterized. Both genes are up-regulated as part of the abscisic acid (ABA) mediated moisture stress response. While AtRD22 transcript was largely restricted to the leaf, that of AtUSPL1 was more prevalent in the root. As the loss of function of either gene increased the plant's moisture stress tolerance, the implication was that their products act to suppress the drought stress response. In addition to the known involvement of AtUSPL1 in seed development, a further role in stress tolerance was demonstrated. Based on transcriptomic data and phenotype we concluded that the enhanced moisture stress tolerance of the two loss-of-function mutants is a consequence of an enhanced basal defense response.

Functional analysis of the ABA-responsive protein family in ABA and stress signal transduction in Arabidopsis

The phytohormone abscisic acid (ABA) plays an important role in plant growth and development, for example in seed dormancy and germination, as well as in plant responses to environmental stresses, such as drought and high salinity. Previous studies have shown that ABA regulates the expression of genes with an ABA-responsive element (ABRE) and their corresponding physiological responses. Bioinformatics analysis identified a GRAM domain-containing gene family that has a multiple ABRE cis-element, which was termed the ABA-responsive protein (ABR) family. To analyze the function of the ABR family, we identified homozygous T-DNA insertion mutants and constructed abr1, 2, 3 double mutants and triple mutant. The abr1, abr2 and abr3 single mutants showed a normal phenotype; however, the germination of seeds of the double mutants and triple mutant were insensitive to ABA, NaCl, mannitol and glucose. ABR1-GFP was distributed as a punctate structure in the cytosol and may be localized in the endomembrane system. The ABR2-GFP and ABR3-GFP proteins localized in the cytoplasm. In addition, ABR1, ABR2 and ABR3 were expressed in various tissues, and could be induced by several abiotic stresses, especially by ABA. The expressions of these genes were significantly suppressed in aba2, abi1 and abi2 null mutants. These results suggested that the ABR family may act downstream of ABI1 and ABI2 in the ABA signal transduction process in plants.

The <I>Popeye</I> Domain-Containing Gene Family

The Popeye domain-containing gene family has been isolated on the basis of a subtractive screen aiming at the identification of novel genes with a heart-restricted gene expression pattern. The gene family codes for membrane proteins containing three transmembrane domains. The carboxy-terminal part of the protein is localized to the cytoplasm and contains a protein domain with high sequence conservation named the Popeye domain. This domain is involved in protein homo dimerization. The gene family is expressed in heart and skeletal muscle cells as well as smooth muscle cells. In addition, Popdc genes are expressed in other cell types such as neuronal cells in restricted areas of the brain, spinal cord, and dorsal root ganglia, and in various epithelial cells. Recently, it has been proposed that Popdc proteins may function as a novel family of adhesion proteins. That the expression pattern has been conserved during evolution and is very similar in all vertebrate classes and also in basal chordates suggests that Popdc proteins play an important role in cardiac and skeletal muscle.

Ege A, a Novel C2 Domain Containing Protein, Is Essential for GPCR-Mediated Gene Expression in Dictyostelium

During early stages of development, expression of aggregative genes in Dictyostelium is regulated by G protein-linked signaling pathways. We have isolated an aggregation-deficient mutant from a restriction enzyme-mediated insertional mutagenesis screen and have obtained its cDNA. Since the mutant expresses prestarvation genes but fails to express early genes, such as cAR1 and GP80, during development, we designated it early gene expression A ( ege A). Ege A, encoding a cytosolic protein of 26 kDa, along with Ege B, belongs to a novel C2 domain-containing gene family. While Ege A mRNA is expressed during the first 2 h of development, Ege B is expressed at later stages. Ege A is not directly required for either G protein-mediated actin polymerization or activation of adenylyl cyclase. Ege A overexpressing and ege A − cells display similar phenotypes, suggesting that an optimal level of Ege A is required for proper function. Constitutive expression of a fully functional cAR1-YFP enables ege A − cells to form loose aggregates, but cAR1-YFP/ ege A − cells are still unable to express GP80, suggesting that losses of gene expression were not solely due to a lack of cAR1. Overexpression of PKAcat, the constitutively active subunit of PKA, does not rescue the ege A − phenotype, suggesting that PKA is not located downstream from Ege A in the signaling pathway. We propose that Ege A is a novel cytosolic component required by early gene expression.

The murine fork head gene Foxn2 is expressed in craniofacial, limb, CNS and somitic tissues during embryogenesis

The fork head domain-containing gene family ( Fox) comprises over 20 members in mammals and is defined by a conserved 110 amino-acid motif containing a winged helix structure DNA-binding domain. The members of this gene family have been implicated as key regulators of embryogenesis, cell cycling, cell lineage restriction and cancer. The Foxn2 gene ( Ches1) is expressed in postgastrulation embryos in multiple tissues that serve as important signaling centers as well as end-stage-differentiated cell types that arise from different germ layers of the developing embryo. The dynamic and specific expression of Foxn2 during embryonic development suggest multiple independent roles for Foxn2 function during gestation.