DNA Methylation Regulates Transcription Factor-Specific Neurodevelopmental but Not Sexually Dimorphic Gene Expression Dynamics in Zebra Finch Telencephalon

Song learning in zebra finches (Taeniopygia guttata) is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized transcriptomic (RNA-sequencing) and epigenomic (RRBS, reduced representation bisulfite sequencing; immunofluorescence) dynamics in matched zebra finch telencephalon samples of both sexes from 1 day post hatching (1 dph) to adulthood, spanning the critical period for song learning (20 and 65 dph). We identified extensive transcriptional neurodevelopmental changes during postnatal telencephalon development. DNA methylation was very low, yet increased over time, particularly in song control nuclei. Only a small fraction of the massive differential expression in the developing zebra finch telencephalon could be explained by differential CpG and CpH DNA methylation. However, a strong association between DNA methylation and age-dependent gene expression was found for various transcription factors (i.e., OTX2, AR, and FOS) involved in neurodevelopment. Incomplete dosage compensation, independent of DNA methylation, was found to be largely responsible for sexually dimorphic gene expression, with dosage compensation increasing throughout life. In conclusion, our results indicate that DNA methylation regulates neurodevelopmental gene expression dynamics through steering transcription factor activity, but does not explain sexually dimorphic gene expression patterns in zebra finch telencephalon.

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In Silico Prediction of Transcription Factor Collaborations Underlying Phenotypic Sexual Dimorphism in Zebrafish (Danio rerio)

Genes ◽

10.3390/genes12060873 ◽

2021 ◽

Vol 12 (6) ◽

pp. 873

Author(s):

Shahrbanou Hosseini ◽

Armin Otto Schmitt ◽

Jens Tetens ◽

Bertram Brenig ◽

Henner Simianer ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Sexual Dimorphism ◽

Sex Determination ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Colour Pattern ◽

Promoter Regions ◽

Dimorphic Gene Expression

The transcriptional regulation of gene expression in higher organisms is essential for different cellular and biological processes. These processes are controlled by transcription factors and their combinatorial interplay, which are crucial for complex genetic programs and transcriptional machinery. The regulation of sex-biased gene expression plays a major role in phenotypic sexual dimorphism in many species, causing dimorphic gene expression patterns between two different sexes. The role of transcription factor (TF) in gene regulatory mechanisms so far has not been studied for sex determination and sex-associated colour patterning in zebrafish with respect to phenotypic sexual dimorphism. To address this open biological issue, we applied bioinformatics approaches for identifying the predicted TF pairs based on their binding sites for sex and colour genes in zebrafish. In this study, we identified 25 (e.g., STAT6-GATA4; JUN-GATA4; SOX9-JUN) and 14 (e.g., IRF-STAT6; SOX9-JUN; STAT6-GATA4) potentially cooperating TFs based on their binding patterns in promoter regions for sex determination and colour pattern genes in zebrafish, respectively. The comparison between identified TFs for sex and colour genes revealed several predicted TF pairs (e.g., STAT6-GATA4; JUN-SOX9) are common for both phenotypes, which may play a pivotal role in phenotypic sexual dimorphism in zebrafish.

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DNA Methylation and Expression Profiles of Whole Blood in Parkinson’s Disease

Frontiers in Genetics ◽

10.3389/fgene.2021.640266 ◽

2021 ◽

Vol 12 ◽

Author(s):

Adrienne R. Henderson ◽

Qi Wang ◽

Bessie Meechoovet ◽

Ashley L. Siniard ◽

Marcus Naymik ◽

...

Keyword(s):

Gene Expression ◽

Parkinson’S Disease ◽

Dna Methylation ◽

Parkinson's Disease ◽

Transcription Factor ◽

Whole Blood ◽

Expression Profiles ◽

Expression Patterns ◽

Motor Deficits ◽

Age Related

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. It is presently only accurately diagnosed at an advanced stage by a series of motor deficits, which are predated by a litany of non-motor symptoms manifesting over years or decades. Aberrant epigenetic modifications exist across a range of diseases and are non-invasively detectable in blood as potential markers of disease. We performed comparative analyses of the methylome and transcriptome in blood from PD patients and matched controls. Our aim was to characterize DNA methylation and gene expression patterns in whole blood from PD patients as a foundational step toward the future goal of identifying molecular markers that could predict, accurately diagnose, or track the progression of PD. We found that differentially expressed genes (DEGs) were involved in the processes of transcription and mitochondrial function and that PD methylation profiles were readily distinguishable from healthy controls, even in whole-blood DNA samples. Differentially methylated regions (DMRs) were functionally varied, including near transcription factor nuclear transcription factor Y subunit alpha (NFYA), receptor tyrosine kinase DDR1, RING finger ubiquitin ligase (RNF5), acetyltransferase AGPAT1, and vault RNA VTRNA2-1. Expression quantitative trait methylation sites were found at long non-coding RNA PAX8-AS1 and transcription regulator ZFP57 among others. Functional epigenetic modules were highlighted by IL18R1, PTPRC, and ITGB2. We identified patterns of altered disease-specific DNA methylation and associated gene expression in whole blood. Our combined analyses extended what we learned from the DEG or DMR results alone. These studies provide a foundation to support the characterization of larger sample cohorts, with the goal of building a thorough, accurate, and non-invasive molecular PD biomarker.

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Molecular regulation of fetal brain development in pigs

10.32469/10355/88112 ◽

2021 ◽

Author(s):

◽

Monica P. Strawn

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Transcription Factor ◽

Brain Development ◽

Early Development ◽

Expression Patterns ◽

Fetal Brain ◽

Molecular Regulation ◽

Fetal Brain Development ◽

The Brain

Two experiments were conducted to investigate molecular regulation that impacts fetal brain development in pigs. In the first experiment (Chapter 2), gene expression was profiled by RNA sequencing (RNA-seq) to examine the whole transcriptome of the male (M) and female (F) fetal brain at gestation day (d) 45, 60 and 90. The analysis showed fewer differentially expressed genes (DEGs) in the brain of male and female fetuses in earlier gestation (d45-d60) when compared to late gestation (d60-d90). The homeobox (HOX) A5 gene that regulates pattern formation in early development was in the top upregulated DEGs between d45 to d60 in fetuses of both sexes. This study also found HOX B5 and D3 genes were in the top upregulated genes between d45 and d60 of the fetal brain of females, but not males. The second experiment (Chapter 3) investigated DNA methylation in pigs. DNA methylation in the fetal brain of both sexes at the same three gestation days was performed by enzymatic methyl sequencing (EM-seq). Hotspots of methylation in specific chromosomal regions were observed in the analysis. The analysis identified 1,475 sites in the pig genome that were methylated in the fetal brain, irrespective of sex, during development. The same sites were methylated in a canonically correlated manner in the blood of the adult stage, both in sows and boars. This is consistent with the Dilman theory of developmental aging (DevAge), which suggests that aging and early development of the brain are regulated by common molecular processes. A comparative analysis (Chapter 4) compared the gene expression patterns in the fetal brain and placenta between pigs and mice. The analysis identified 112 genes that were expressed (mean FPKM > 10) in the fetal brain of both species but not expressed (mean FPKM < 1) in the placenta of either species, and 10 genes that were expressed in the placenta of both species but not expressed in the fetal brain. In-silico analysis of the transcription factor binding sites in the 500 bp of the upstream DNA of these common genes revealed that they were commonly regulated by the RE1 silencing transcription factor (REST), which is a multifaceted transcription factor that acts as a master regulator of neurogenesis as well as controls neural excitation and the aging processes.

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Response of wheat DREB transcription factor to drought stress based on DNA methylation

10.21203/rs.2.22506/v4 ◽

2021 ◽

Author(s):

Yanqiu Zhu ◽

Huihui Wang ◽

Wenjing Jia ◽

Xiaoyan Wei ◽

Zhikun Duan ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Transcription Factor ◽

Drought Stress ◽

Promoter Methylation ◽

Expression Patterns ◽

Dreb Transcription Factor ◽

The Status ◽

Element Binding Protein ◽

Responsive Element

Abstract Background: The growth and development of wheat are seriously influenced by drought, dehydration responsive element binding protein (DREB) plays an important role in the response of plant to drought stress, but epigenetic regulation for gene expression of DREB transcription factor is less studied, especially the regulatory role of DNA methylation has not been reported.Results: In this research, DREB2, DREB6 and Wdreb2 were cloned from wheat AK58, and one 712-bp intron was identified in DREB6. Although AP2/EREBP domains of DREB2, DREB6 and Wdreb2 showed 73.25% identity, they belong to different types of DREB transcription factor. Under drought stress, different transcript expression patterns of DREB2, DREB6 and Wdreb2 were observed, and their expression had tissue specificity, was obviously higher in leaves. Promoters of DREB2, DREB6 and Wdreb2 were further studied, some elements related to stresses were found, and the promoters of DREB2 and Wdreb2 were slightly methylated, but DREB6 promoter was moderately methylated. Compared with the control, the level of promoter methylation in DREB2 and DREB6 decreased after 2 h stress treatment, and then increased, which was opposite in Wdreb2 promoter, the status of promoter methylation in DREB2, DREB6 and Wdreb2 also had significant changes under drought stress. Further analysis showed that promoter methylation of DREB6 and Wdreb2 was negatively correlated with their expression, especially in Wdreb2. Conclusions: Our data suggest the different functions of DREB2, DREB6 and Wdreb2 in response to drought stress, and demonstrate the strong effects of promoter methylation on the regulation of Wdreb2 and DREB6 gene expression.

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Faculty Opinions recommendation of Contrasting effects of different maternal diets on sexually dimorphic gene expression in the murine placenta.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2556956.2209054 ◽

2010 ◽

Author(s):

Sandra Davidge ◽

Stephane Bourque

Keyword(s):

Gene Expression ◽

Sexually Dimorphic ◽

Dimorphic Gene Expression

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Gene expression profiling of epigenetic chromatin modification enzymes and histone marks by cigarette smoke: implications for COPD and lung cancer

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00253.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. L1245-L1258 ◽

Cited By ~ 19

Author(s):

Isaac K. Sundar ◽

Irfan Rahman

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Dna Methylation ◽

Cigarette Smoke ◽

Histone Modifications ◽

Expression Patterns ◽

Chromatin Modification ◽

Gene Expression Patterns ◽

Validation Data ◽

Histone Marks

Chromatin-modifying enzymes mediate DNA methylation and histone modifications on recruitment to specific target gene loci in response to various stimuli. The key enzymes that regulate chromatin accessibility for maintenance of modifications in DNA and histones, and for modulation of gene expression patterns in response to cigarette smoke (CS), are not known. We hypothesize that CS exposure alters the gene expression patterns of chromatin-modifying enzymes, which then affects multiple downstream pathways involved in the response to CS. We have, therefore, analyzed chromatin-modifying enzyme profiles and validated by quantitative real-time PCR (qPCR). We also performed immunoblot analysis of targeted histone marks in C57BL/6J mice exposed to acute and subchronic CS, and of lungs from nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). We found a significant increase in expression of several chromatin modification enzymes, including DNA methyltransferases, histone acetyltransferases, histone methyltransferases, and SET domain proteins, histone kinases, and ubiquitinases. Our qPCR validation data revealed a significant downregulation of Dnmt1, Dnmt3a, Dnmt3b, Hdac2, Hdac4, Hat1, Prmt1, and Aurkb. We identified targeted chromatin histone marks (H3K56ac and H4K12ac), which are induced by CS. Thus CS-induced genotoxic stress differentially affects the expression of epigenetic modulators that regulate transcription of target genes via DNA methylation and site-specific histone modifications. This may have implications in devising epigenetic-based therapies for COPD and lung cancer.

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Sexually dimorphic gene expression and transcriptome evolution provide mixed evidence for a fast-Z effect in Heliconius

Journal of Evolutionary Biology ◽

10.1111/jeb.13410 ◽

2019 ◽

Vol 32 (3) ◽

pp. 194-204 ◽

Cited By ~ 10

Author(s):

Ana Pinharanda ◽

Marjolaine Rousselle ◽

Simon H. Martin ◽

Joe J. Hanly ◽

John W. Davey ◽

...

Keyword(s):

Gene Expression ◽

Sexually Dimorphic ◽

Dimorphic Gene Expression

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An integrative multi-omics approach in Sjögren’s Syndrome identifies novel genetic drivers with regulatory function and disease-specificity

10.1101/2020.09.14.20192211 ◽

2020 ◽

Author(s):

María Teruel ◽

Guillermo Barturen ◽

Manuel Martínez-Bueno ◽

Miguel Barroso ◽

Olivia Castelli ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Sjögren’S Syndrome ◽

Genetic Variants ◽

Sjögren's Syndrome ◽

Expression Patterns ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Regulatory Function ◽

Sjögren‘S Syndrome

ABSTRACTPrimary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study we identified vast coordinated hypomethylation and overexpression effects, that also exhibit increased variability, in many already known IFN-regulated genes. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of novel genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified new genetic variants associated with SS that mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, DNA methylation, gene expression and SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.

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