Regulation Of Gene Activity Research Articles

Lymphatic-derived oxysterols promote anti-tumor immunity and response to immunotherapy in melanoma.

In melanoma, lymphangiogenesis correlates with metastasis and poor prognosis and promotes immunosuppression. However, it also potentiates immunotherapy by supporting immune cell trafficking. We show in a lymphangiogenic murine melanoma that lymphatic endothelial cells (LECs) upregulate the enzyme Ch25h, which catalyzes the formation of 25-hydroxycholesterol (25-HC) from cholesterol and plays important roles in lipid metabolism, gene regulation, and immune activation. We identify a role for LECs as a source of extracellular 25-HC in tumors inhibiting PPAR-γ in intra-tumoral macrophages and monocytes, preventing their immunosuppressive function and instead promoting their conversion into proinflammatory myeloid cells that support effector T cell functions. In human melanoma, LECs also upregulate Ch25h, and its expression correlates with the lymphatic vessel signature, infiltration of pro-inflammatory macrophages, better patient survival, and better response to immunotherapy. We identify here in mechanistic detail an important LEC function that supports anti-tumor immunity, which can be therapeutically exploited in combination with immunotherapy.

Nuclear Argonaute protein NRDE-3 switches small RNA partners during embryogenesis to mediate temporal-specific gene regulatory activity.

RNA interference (RNAi) is a conserved gene regulation mechanism that utilizes the Argonaute protein and their associated small RNAs to exert regulatory function on complementary transcripts. While the majority of germline-expressed RNAi pathway components reside in perinuclear germ granules, it is unknown whether and how RNAi pathways are spatially organized in other cell types. Here we find that the small RNA biogenesis machinery is spatially and temporally organized during embryogenesis. Specifically, the RNAi factor, SIMR-1, forms visible concentrates during mid-embryogenesis that contain an RNA-dependent RNA polymerase, a poly-UG polymerase, and the unloaded nuclear Argonaute protein, NRDE-3. We also observe that many other RNAi factors form foci in embryonic cells distinct from "SIMR granules", including the Argonaute protein CSR-1, underscoring a potential role for cytoplasmic concentrates of RNAi factors to promote gene regulation in embryos. Curiously, coincident with the appearance of the SIMR granules, the small RNAs bound to NRDE-3 switch from predominantly CSR-class 22G-RNAs to ERGO-dependent 22G-RNAs. Prior work has shown that NRDE-3 binds ERGO-dependent 22G-RNAs in the somatic cells of larvae and adults to silence ERGO-target genes; here we demonstrate that NRDE-3-bound, CSR-class 22G-RNAs repress transcription in oocytes. Thus, our study defines two separable roles for NRDE-3, targeting germline-expressed genes during oogenesis to promote global transcriptional repression, and switching during embryogenesis to repress recently duplicated genes and retrotransposons in somatic cells, highlighting the plasticity of Argonaute proteins and the need for more precise temporal characterization of Argonaute-small RNA interactions.

Potenciál využití molekulárních analýz pro genetickou charakterizaci rezistentních jedinců borovice lesní (Pinus sylvestris L.)

Scots pine (Pinus sylvestris L.) is one of the most important economic trees with deteriorating health conditions observed in recent years. The work aimed to compare and evaluate the regulation of gene activities involved in defense mechanisms under biotic and abiotic stress conditions in a group of healthy individuals of Scots pine and individuals damaged by the pine beetle (Phaenops cyanea). Determination of the relative gene expression levels of twelve selected genes was carried out by qPCR analysis in samples of Scots pine needles collected at two localities, Stará Boleslav and Podbrahy. At both monitored locations we noted the same trends in the regulation of the relative gene expression profile for seven genes (CHS, CH5B, PR_P2, PO12, PAAL, SUCSYN3 and USP A), including a significant increase in the relative gene expression level of the phenylalanine-ammonia lyase (PAAL) involved in the biosynthesis of flavonoids, phenylpropanoids and lignin in plants, in the group of damaged individuals compared to the control group at the locality Stará Boleslav. For both groups of samples (healthy and damaged individuals) we noticed considerable variability in the measured data related to many variable factors of the external environment and the genotype of each individual, even when comparing both habitats.

Using Callus as an Ex Vivo System for Chromatin Analysis.

Next-generation sequencing has revolutionized epigenetics research, enabling a comprehensive analysis of DNA methylation and histone modification profiles to explore complex biological systems at unprecedented depth. Deciphering the intricate epigenetic mechanisms that regulate gene activity presents significant challenges, including the issue of analyzing heterogeneous cell populations in bulk. Bulk analysis introduces bias and can obscure crucial information by averaging readouts from distinct cells. Various approaches have been developed to address this issue, such as cell-type-specific enrichment or single-cell sequencing techniques. However, the need for transgenic lines with fluorescent markers, along with technical challenges such as efficient protoplast isolation and low yield, limits their widespread adoption and use in multi-omic studies. This review discusses the pros and cons of these approaches, providing a valuable basis for selecting the most suitable strategy to minimize heterogeneity. We will also highlight the use of cotyledon-derived callus as an ex vivo system as a simple, accessible, and robust platform for enabling high-throughput multi-omic analyses.

Remodeling the Epigenome Through Meditation: Effects on Brain, Body, and Well-being.

Epigenetic mechanisms are key processes that constantly reshape genome activity carrying out physiological responses to environmental stimuli. Such mechanisms regulate gene activity without modifying the DNA sequence, providing real-time adaptation to changing environmental conditions. Both favorable and unfavorable lifestyles have been shown to influence body and brain by means of epigenetics, leaving marks on the genome that can either be rapidly reversed or persist in time and even be transmitted trans-generationally. Among virtuous habits, meditation seemingly represents a valuable way of activating inner resources to cope with adverse experiences. While unhealthy habits, stress, and traumatic early-life events may favor the onset of diseases linked to inflammation, neuroinflammation, and neuroendocrine dysregulation, the practice of mindfulness-based techniques was associated with the alleviation of many of the above symptoms, underlying the importance of lifestyles for health and well-being. Meditation influences brain and body systemwide, eliciting structural/morphological changes as well as modulating the levels of circulating factors and the expression of genes linked to the HPA axis and the immune and neuroimmune systems. The current chapter intends to give an overview of pioneering research showing how meditation can promote health through epigenetics, by reshaping the profiles of the three main epigenetic markers, namely DNA methylation, histone modifications, and non-coding RNAs.

Integrating multiple single-cell multi-omics samples with Smmit.

Multi-sample single-cell multi-omics datasets, which simultaneously measure multiple data modalities in the same cells across multiple samples, facilitate the study of gene expression, gene regulatory activities, and protein abundances on a population scale. We developed Smmit, a computational method for integrating data both across samples and modalities. Compared to existing methods, Smmit more effectively removes batch effects while preserving relevant biological information, resulting in superior integration outcomes. Additionally, Smmit is more computationally efficient and builds upon existing computational pipelines, requiring minimal effort for implementation. Smmit is an R software package that is freely available on Github: https://github.com/zji90/Smmit .

Advancing public understanding of epigenetics: the EPIBOOST project’s video science outreach

ABSTRACT The public’s growing interest in epigenetics, particularly its applications in human health, underscores the significance of epigenetic mechanisms in regulating gene activity and promoting phenotypic diversity without altering DNA sequences. Within the framework of the Extended Evolutionary Synthesis, epigenetics is regarded as a non-genetic contributor to evolution. The EPIBOOST project, “BOOSting excellence in environmental EPIgenetics,” investigates epigenetic changes induced by contaminants in aquatic organisms and aims to enhance public understanding of epigenetics through science outreach videos. A multidisciplinary team comprising Biology, Education, and Design researchers produced the video “What is Epigenetics?” using a design-based research methodology and a design thinking approach. This process involved storyboard design, audio recording, image production, video editing, testing, refinement, and public dissemination. The interactive development of the storyboard and script aimed to efficiently communicate the significance of epigenetics, fostering public understanding of this emerging research area through an effective science communication strategy. This paper focuses on the development process for the first video, which aims to promote public awareness of epigenetics using the AEIOU framework (Awareness, Enjoyment, Interest, Opinions, and Understanding) to elucidate epigenetic concepts such as DNA methylation, gene expression, and phenotype, and their integration in environmental assessment frameworks.

Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.

The p53 family of transcription factors (p53, p63 and p73) regulate diverse organismal processes including tumor suppression, maintenance of genome integrity and the development of skin and limbs. Crosstalk between transcription factors with highly similar DNA binding profiles, like those in the p53 family, can dramatically alter gene regulation. While p53 is primarily associated with transcriptional activation, p63 mediates both activation and repression. The specific mechanisms controlling p63-dependent gene regulatory activity are not well understood. Here, we use massively parallel reporter assays (MPRA) to investigate how local DNA sequence context influences p63-dependent transcriptional activity. Most regulatory elements with a p63 response element motif (p63RE) activate transcription, although binding of the p63 paralog, p53, drives a substantial proportion of that activity. p63RE sequence content and co-enrichment with other known activating and repressing transcription factors, including lineage-specific factors, correlates with differential p63RE-mediated activities. p63 isoforms dramatically alter transcriptional behavior, primarily shifting inactive regulatory elements towards high p63-dependent activity. Our analysis provides novel insight into how local sequence and cellular context influences p63-dependent behaviors and highlights the key, yet still understudied, role of transcription factor paralogs and isoforms in controlling gene regulatory element activity.

Associations between DNA methylation and cognitive function in early-stage hormone receptor-positive breast cancer patients.

Approximately one-third of breast cancer (BC) patients show poorer cognitive function (CF) before receiving adjuvant therapy compared with age-matched healthy controls. However, the biological mechanisms driving CF variation in the context of BC remain unclear. In this study, we aimed to identify genes and biological pathways associated with CF in postmenopausal women with early-stage hormone receptor-positive (HR+) BC using DNA methylation (DNAm) data, a dynamic regulator of gene activity. Epigenome-wide association studies (EWAS) and differentially methylated region analyses were performed for each CF phenotype (seven objective domains and one subjective phenotype) using DNAm data from whole blood samples (n=109) taken at time of enrollment. Post-EWAS functional analyses were performed to enhance the understanding of the CF-related cytosine-phosphate-guanine (CpG) sites. When adjusting for age, verbal IQ scores, and global DNAm signature, cg10331779 near CTNND2 (p-value= 9.65 × 10 -9 ) and cg25906741 in MLIP (p-value= 2.01 × 10 -8 ) were associated with processing speed and subjective CF, respectively, while regions in/near SLC6A11 , PRKG1/CSTF2T , and FAM3B for processing speed, and regions in/near PI4KB and SGCE/PEG10 for mental flexibility were differentially methylated. In addition, beta-estradiol was identified as a common upstream regulator for all the CF phenotypes, suggesting an essential role of estrogen in explaining variation in CF of HR+ BC patients. In our EWAS of 8 CF phenotypes, we found two epigenome-wide significant signals, one at cg10331779 near CTNND2 with processing speed and the other at cg25906741 in MLIP with subjective CF. We also found three differentially methylated regions associated with processing speed and two associated with mental flexibility. These findings need replication in larger cohorts.

Comparative Genomics Provides Insights into Adaptive Evolution and Demographics of Bats.

Bats possess a range of distinctive characteristics, including flight, echolocation, impressive longevity, and the ability to harbor various zoonotic pathogens. Additionally, they account for the second-highest species diversity among mammalian orders, yet their phylogenetic relationships and demographic history remain underexplored. Here, we generated de novo assembled genomes for 17 bat species and 2 of their mammalian relatives (the Amur hedgehog and Chinese mole shrew), with 12 genomes reaching chromosome-level assembly. Comparative genomics and ChIP-seq assays identified newly gained genomic regions in bats potentially linked to the regulation of gene activity and expression. Notably, some antiviral infection-related gene under positive selection exhibited the activity of suppressing cancer, evidencing the linkage between virus tolerance and cancer resistance in bats. By integrating published bat genome assemblies, phylogenetic reconstruction established the proximity of noctilionoid bats to vesper bats. Interestingly, we found 2 distinct patterns of ancient population dynamics in bats and population changes since the last glacial maximum does not reflect species phylogenetic relationships. These findings enriched our understanding of adaptive mechanisms and demographic history of bats.

Characterising developmental dynamics of adult epigenetic clock sites

DNA methylation (DNAm), an epigenetic mechanism that regulates gene activity in response to genetic and environmental influences, changes as we age. DNAm at specific sites on the genome can be used to calculate 'epigenetic clocks', which are powerful biomarkers of age, as well as of ageing. However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life. This knowledge could be used to optimise healthy ageing well before the onset of age-related conditions. We leveraged results from two longitudinal population-based cohorts (N=5019 samples from 2348 individuals) to characterise trajectories of adult clock sites from birth to early adulthood. To explore what factors may drive early individual differences at these clock sites, we also tested for enrichment of genetic factors and prenatal exposures based on existing epigenome-wide association meta-analyses. We find that clock sites (i) diverge widely in their developmental trajectories, often showing non-linear change over time; (ii) are substantially more likely than non-clock sites to vary between individuals already from birth, differences that are predictive of DNAm variation at later ages; and (iii) show enrichment for genetic influences and prenatal environmental exposures, including prenatal smoking, diet and maternal physical health conditions. These results suggests that age(ing)-related epigenetic processes might originate-and differ between individuals-already very early in development. Understanding what drives these differences may in future help us to devise better strategies to promote healthy ageing. This research was conducted while C.A.M.C. was a Hevolution/AFAR New Investigator Awardee in Aging Biology and Geroscience Research. Full personal funding details, as well as cohort funding details, can be found in the Acknowledgements.

Two riboswitch classes that share a common ligand-binding fold show major differences in the ability to accommodate mutations.

Riboswitches are structured RNAs that sense small molecules to control expression. Prequeuosine1 (preQ1)-sensing riboswitches comprise three classes (I, II and III) that adopt distinct folds. Despite this difference, class II and III riboswitches each use 10 identical nucleotides to bind the preQ1 metabolite. Previous class II studies showed high sensitivity to binding-pocket mutations, which reduced preQ1 affinity and impaired function. Here, we introduced four equivalent mutations into a class III riboswitch, which maintained remarkably tight preQ1 binding.Co-crystal structures of each class III mutant showed compensatory interactions that preserve the fold. Chemical modification analysis revealed localized RNA flexibility changes for each mutant, but molecular dynamics (MD) simulations suggested that each mutation was not overtly destabilizing. Although impaired, class III mutants retained tangible gene-regulatory activity in bacteria compared to equivalent preQ1-II variants; mutations in the preQ1-pocket floor were tolerated better than wall mutations. Principal component analysis of MD trajectories suggested that the most functionally deleterious wall mutation samples different motions compared to wildtype. Overall, the results reveal that formation of compensatory interactions depends on the context of mutations within the overall fold and that functionally deleterious mutations can alter long-range correlated motions that link the riboswitch binding pocket with distal gene-regulatory sequences.

A comprehensive review on the role of Vitamin A on human health and nutrition

Vitamin A is a crucial nutrient that protects the body from oxidative stress caused by free radicals, which are unstable molecules that can damage cellular components. Its antioxidant properties helps maintaining various physiological functions that depend on its presence, including vision, immune function and skin health. The human body can convert natural forms of vitamin A (retinol, retinal and retinoic acid) and provitamin A (β-carotene) into active forms, which interact with specific molecular targets, influencing gene expression, cell differentiation and cellular processes. This comprehensive review provides an in-depth examination of vitamin A, covering its dietary sources, physiological roles and consequences of deficiency. In this research review explored the metabolic pathways of vitamin A, including absorption, transport and storage, as well as its potential applications, offering a thorough understanding of this essential nutrient. Furthermore, we have decreased the latest research on vitamin A's role in, maintaining healthy vision, immune function, and skin health, treating various diseases and conditions, such as retinal disorders, infectious diseases and cancer, mechanisms of action, including gene regulation, cell signaling, and antioxidant activity, relationships with other nutrients and health outcomes, including vitamin D, iron, and zinc, impact of deficiency on human health, including night blindness, impaired immunity, and skin disorders and emerging research on potential benefits and risks, including its role in chronic diseases and interactions with medications. Key words: Nutrition, retinyl ester, Nyctalopia, Rhodopsin, Vitamin A, β-carotene

Large-scale multi-omic analysis identifies noncoding somatic driver mutations and nominates ZFP36L2 as a driver gene for pancreatic ductal adenocarcinoma.

Identification of somatic driver mutations in the noncoding genome remains challenging. To comprehensively characterize noncoding driver mutations for pancreatic ductal adenocarcinoma (PDAC), we first created genome-scale maps of accessible chromatin regions (ACRs) and histone modification marks (HMMs) in pancreatic cell lines and purified pancreatic acinar and duct cells. Integration with whole-genome mutation calls from 506 PDACs revealed 314 ACRs/HMMs significantly enriched with 3,614 noncoding somatic mutations (NCSMs). Functional assessment using massively parallel reporter assays (MPRA) identified 178 NCSMs impacting reporter activity (19.45% of those tested). Focused luciferase validation confirmed negative effects on gene regulatory activity for NCSMs near CDKN2A and ZFP36L2 . For the latter, CRISPR interference (CRISPRi) further identified ZFP36L2 as a target gene (16.0 - 24.0% reduced expression, P = 0.023-0.0047) with disrupted KLF9 binding likely mediating the effect. Our integrative approach provides a catalog of potentially functional noncoding driver mutations and nominates ZFP36L2 as a PDAC driver gene.

The regulatory functions of ESX-1 substrates, EspE and EspF, are separable from secretion.

Pathogenic mycobacteria are a significant global health burden. The ESX-1 secretion system is essential for mycobacterial pathogenesis. The secretion of ESX-1 substrates is required for phagosomal lysis, which allows the bacteria to enter the macrophage cytoplasm, induce a Type I IFN response, and spread to new host cells. EspE and EspF are dual-functioning ESX-1 substrates. Inside the mycobacterial cell, they regulate transcription of ESX-1-associated genes. Following secretion, EspE and EspF are essential for lytic activity. The link between EspE/F secretion and regulatory function has not been investigated. We investigated the relationship between EspE and EspF using molecular genetics in Mycobacterium marinum, a non-tuberculous mycobacterial species that serves as an established model for ESX-1 secretion and function in Mycobacterium tuberculosis. Our data support that EspE and EspF, which require each other for secretion, directly interact. The disruption of the predicted protein-protein interaction abrogates hemolytic activity and secretion but does not impact their gene regulatory activities in the mycobacterial cell. In addition, we predict a direct protein-protein interaction between the EsxA/EsxB heterodimer and EspF. Our data support that the EspF/EsxA interaction is also required for hemolytic activity and EspE secretion. Our study sheds light on the intricate molecular mechanisms governing the interactions between ESX-1 substrates, regulatory function, and ESX-1 secretion, moving the field forward.IMPORTANCETuberculosis (TB), caused by Mycobacterium tuberculosis, is a historical and pervasive disease responsible for millions of deaths annually. The rise of antibiotic and treatment-resistant TB, as well as the rise of infection by non-tuberculous mycobacterial species, calls for a better understanding of pathogenic mycobacteria. The ESX-1 secreted substrates, EspE and EspF, are required for mycobacterial virulence and may be responsible for phagosomal lysis. This study focuses on the mechanism of EspE and EspF secretion from the mycobacterial cell.

Single Cell Profiling in the Sox10 Dom/+ Hirschsprung Mouse Implicates Hoxa6 in Enteric Neuron Lineage Allocation.

Enteric nervous system (ENS) development requires migration, proliferation, and appropriate neuronal diversification from progenitors to enable normal gastrointestinal (GI) motility. Sox10 deficit causes aganglionosis, modeling Hirschsprung disease, and disrupts ratios of postnatal enteric neurons in proximal ganglionated bowel. How Sox10 deficiency alters ratios of enteric neuron subtypes is unclear. Sox10's prominent expression in enteric neural crest-derived progenitors (ENCP) and lack of this gene in enteric neurons led us to examine Sox10 Dom effects ENS progenitors and early differentiating enteric neurons. ENS progenitors, developing neurons, and enteric glia were isolated from Sox10 +/+ and Sox10 Dom/+ littermates for single-cell RNA sequencing (scRNA-seq). scRNA-seq data was processed to identify cell type-specific markers, differentially expressed genes, cell fate trajectories, and gene regulatory network activity between genotypes. Hybridization chain reaction (HCR) validated expression changes detected in scRNA-seq. scRNA-seq profiles revealed three neuronal lineages emerging from cycling progenitors via two transition pathways accompanied by elevated activity of Hox gene regulatory networks (GRN) as progenitors transition to neuronal fates. Sox10 Dom/+ scRNA-seq profiles exhibited a novel progenitor cluster, decreased abundance of cells in transitional states, and shifts in cell distributions between two neuronal trajectories. Hoxa6 was differentially expressed in the neuronal lineages impacted in Sox10 Dom/+ mutants and HCR identified altered Hoxa6 expression in early developing neurons of Sox10 Dom/+ ENS. Sox10 Dom/+ mutation shifts enteric neuron types by altering neuronal trajectories during early ENS lineage segregation. Multiple neurogenic transcription factors are reduced in Sox10 Dom/+ scRNA-seq profiles including multiple Hox genes. This is the first report that implicates Hox genes in lineage diversification of enteric neurons.

Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by progressive memory loss and cognitive decline, affecting behavior, speech, and motor abilities. The neuropathology of AD includes the formation of extracellular amyloid-β plaque and intracellular neurofibrillary tangles of phosphorylated tau, along with neuronal loss. While neuronal loss is an AD hallmark, cell-cell communication between neuronal and non-neuronal cell populations maintains neuronal health and brain homeostasis. To study changes in cellcell communication during disease progression, we performed snRNA-sequencing of the hippocampus from female 3xTg-AD and wild-type littermates at 6 and 12 months. We inferred differential cell-cell communication between 3xTg-AD and wild-type mice across time points and between senders (astrocytes, microglia, oligodendrocytes, and OPCs) and receivers (excitatory and inhibitory neurons) of interest. We also assessed the downstream effects of altered glia-neuron communication using pseudobulk differential gene expression, functional enrichment, and gene regulatory analyses. We found that glia-neuron communication is increasingly dysregulated in 12-month 3xTg-AD mice. We also identified 23 AD-associated ligand-receptor pairs that are upregulated in the 12-month-old 3xTg-AD hippocampus. Our results suggest increased AD association of interactions originating from microglia. Signaling mediators were not significantly differentially expressed but showed altered gene regulation and TF activity. Our findings indicate that altered glia-neuron communication is increasingly dysregulated and affects the gene regulatory mechanisms in neurons of 12-month-old 3xTg-AD mice.

Allelic effects on KLHL17 expression likely mediated by JunB/D underlie a PDAC GWAS signal at chr1p36.33.

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the U.S. Both rare and common germline variants contribute to PDAC risk. Here, we fine-map and functionally characterize a common PDAC risk signal at 1p36.33 (tagged by rs13303010) identified through a genome wide association study (GWAS). One of the fine-mapped SNPs, rs13303160 (r2=0.93 in 1000G EUR samples, OR=1.23, P value=2.74x10-9) demonstrated allele-preferential gene regulatory activity in vitro and allele-preferential binding of JunB and JunD in vitro and in vivo. Expression Quantitative Trait Locus (eQTL) analysis identified KLHL17 as a likely target gene underlying the signal. Proteomic analysis identified KLHL17 as a member of the Cullin-E3 ubiquitin ligase complex in PDAC-derived cells. In silico differential gene expression analysis of the GTExv8 pancreas data suggested an association between lower KLHL17 (risk associated) and pro-inflammatory pathways. We hypothesize that KLHL17 may mitigate inflammation by recruiting pro-inflammatory proteins for ubiquitination and degradation thereby influencing PDAC risk.

Establishment of single-cell transcriptional states during seed germination

Germination involves highly dynamic transcriptional programs as the cells of seeds reactivate and express the functions necessary for establishment in the environment. Individual cell types have distinct roles within the embryo, so must therefore have cell type-specific gene expression and gene regulatory networks. We can better understand how the functions of different cell types are established and contribute to the embryo by determining how cell type-specific transcription begins and changes through germination. Here we describe a temporal analysis of the germinating Arabidopsis thaliana embryo at single-cell resolution. We define the highly dynamic cell type-specific patterns of gene expression and how these relate to changing cellular function as germination progresses. Underlying these are unique gene regulatory networks and transcription factor activity. We unexpectedly discover that most embryo cells transition through the same initial transcriptional state early in germination, even though cell identity has already been established during embryogenesis. Cells later transition to cell type-specific gene expression patterns. Furthermore, our analyses support previous findings that the earliest events leading to the induction of seed germination take place in the vasculature. Overall, our study constitutes a general framework with which to characterize Arabidopsis cell transcriptional states through seed germination, allowing investigation of different genotypes and other plant species whose seed strategies may differ.

On the Cancer

This article theoretically speculates that after replication of a pair of DNA they must be allocated to two daughter cells in a transverse division or erect division manner. Transverse division represents differentiation, while erect division represents transformation. The molecular structure determines that DNA has greater hydrophobicity than RNA. The hydrophobic modification of chromatin regulates gene activity and centromere similarity between new and old DNA. A difference in division between cancer cells and embryonic stem cells is discussed