Integrated analysis of transcriptome and histone modifications in granulosa cells during ovulation in female mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Yuichiro Shirafuta ◽  
Isao Tamura ◽  
Yasuyuki Ohkawa ◽  
Ryo Maekawa ◽  
Yumiko Doi-Tanaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Inflammatory Response ◽  
Histone Modifications ◽  
Granulosa Cells ◽  
Cellular Functions ◽  
Lh Surge ◽  
Genome Wide ◽  
Ros Metabolism ◽  
Rapid Changes

Abstract The ovulatory luteinizing hormone (LH) surge induces rapid changes of gene expression and cellular functions in granulosa cells (GCs) undergoing luteinization. However, it remains unclear how the changes in genome-wide gene expression are regulated. H3K4me3 histone modifications are involved in rapid alteration of gene expression. In this study, we investigated genome-wide changes of transcriptome and H3K4me3 status in mouse GCs undergoing luteinization. GCs were obtained from mice treated with equine chorionic gonadotropin (eCG) before, 4 h and 12 h after human (h)CG injection. RNA-sequencing identified a number of up- and down-regulated genes, which could be classified into eight patterns according to the time-course changes of gene expression. Many genes were transiently up- or down-regulated at 4 h after hCG stimulation. Gene ontology terms associated with these genes included steroidogenesis, ovulation, COC expansion, angiogenesis, immune system, ROS metabolism, inflammatory response, metabolism and autophagy. The cellular functions of DNA repair and cell growth were newly identified as being activated during ovulation. ChIP-sequencing revealed a genome-wide and rapid change of H3K4me3 during ovulation. Integration of transcriptome and H3K4me3 data identified many H3K4me3-associated genes that are involved in steroidogenesis, ovulation, COC expansion, angiogenesis, inflammatory response, immune system, ROS metabolism, lipid and glucose metabolism, autophagy, and regulation of cell size. The present results suggest that genome-wide changes in H3K4me3 after the LH surge are associated with rapid changes in gene expression in GCs, which enables GCs acquire a lot of cellular functions within a short time that are required for ovulation and luteinization.

scholarly journals Changes in Histone Modification and DNA Methylation of the StAR and Cyp19a1 Promoter Regions in Granulosa Cells Undergoing Luteinization during Ovulation In Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 458-470 ◽  
Author(s):  
Lifa Lee ◽  
Hiromi Asada ◽  
Fumie Kizuka ◽  
Isao Tamura ◽  
Ryo Maekawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Granulosa Cells ◽  
Chromatin Immunoprecipitation ◽  
Binding Protein ◽  
Mrna Levels ◽  
Chromatin Immunoprecipitation Assay ◽  
Immunoprecipitation Assay ◽  
Rapid Changes

The ovulatory LH surge induces rapid up-regulation of steroidogenic acute regulatory (StAR) protein and rapid down-regulation of aromatase (Cyp19a1) in granulosa cells (GCs) undergoing luteinization during ovulation. This study investigated in vivo whether epigenetic mechanisms including histone modifications are involved in the rapid changes of StAR and Cyp19a1 gene expression. GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and after human (h)CG injection. StAR mRNA levels rapidly increased after hCG injection, reached a peak at 4 h, and then remained higher compared with 0 h until 12 h. Cyp19a1 mRNA levels gradually decreased after hCG injection and reached their lowest level at 12 h. A chromatin immunoprecipitation assay revealed that levels of histone-H4 acetylation (Ac-H4) and trimethylation of histone-H3 lysine-4 (H3K4me3) increased whereas H3K9me3 and H3K27me3 decreased in the StAR promoter after hCG injection. On the other hand, the levels of Ac-H3 and -H4 and H3K4me3 decreased, and H3K27me3 increased in the Cyp19a1 promoter after hCG injection. Chromatin condensation, which was analyzed using deoxyribonuclease I, decreased in the StAR promoter and increased in the Cyp19a1 promoter after hCG injection. A chromatin immunoprecipitation assay also showed that binding activities of CAATT/enhancer-binding protein β to the StAR promoter increased and binding activities of phosphorylated-cAMP response element binding protein to the Cyp19a1 promoter decreased after hCG injection. These results provide in vivo evidence that histone modifications are involved in the rapid changes of StAR and Cyp19a1 gene expression by altering chromatin structure of the promoters in GCs undergoing luteinization during ovulation.

scholarly journals Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen Candida albicans

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Robert Jordan Price ◽  
Esther Weindling ◽  
Judith Berman ◽  
Alessia Buscaino
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Histone Modifications ◽  
Chromatin Structure ◽  
Fungal Pathogen ◽  
Histone H3 ◽  
Content Type ◽  
Chromatin States ◽  
Genome Wide ◽  
Chromatin Profiling

ABSTRACT Eukaryotic genomes are packaged into chromatin structures that play pivotal roles in regulating all DNA-associated processes. Histone posttranslational modifications modulate chromatin structure and function, leading to rapid regulation of gene expression and genome stability, key steps in environmental adaptation. Candida albicans, a prevalent fungal pathogen in humans, can rapidly adapt and thrive in diverse host niches. The contribution of chromatin to C. albicans biology is largely unexplored. Here, we generated the first comprehensive chromatin profile of histone modifications (histone H3 trimethylated on lysine 4 [H3K4me3], histone H3 acetylated on lysine 9 [H3K9Ac], acetylated lysine 16 on histone H4 [H4K16Ac], and γH2A) across the C. albicans genome and investigated its relationship to gene expression by harnessing genome-wide sequencing approaches. We demonstrated that gene-rich nonrepetitive regions are packaged into canonical euchromatin in association with histone modifications that mirror their transcriptional activity. In contrast, repetitive regions are assembled into distinct chromatin states; subtelomeric regions and the ribosomal DNA (rDNA) locus are assembled into heterochromatin, while major repeat sequences and transposons are packaged in chromatin that bears features of euchromatin and heterochromatin. Genome-wide mapping of γH2A, a marker of genome instability, identified potential recombination-prone genomic loci. Finally, we present the first quantitative chromatin profiling in C. albicans to delineate the role of the chromatin modifiers Sir2 and Set1 in controlling chromatin structure and gene expression. This report presents the first genome-wide chromatin profiling of histone modifications associated with the C. albicans genome. These epigenomic maps provide an invaluable resource to understand the contribution of chromatin to C. albicans biology and identify aspects of C. albicans chromatin organization that differ from that of other yeasts. IMPORTANCE The fungus Candida albicans is an opportunistic pathogen that normally lives on the human body without causing any harm. However, C. albicans is also a dangerous pathogen responsible for millions of infections annually. C. albicans is such a successful pathogen because it can adapt to and thrive in different environments. Chemical modifications of chromatin, the structure that packages DNA into cells, can allow environmental adaptation by regulating gene expression and genome organization. Surprisingly, the contribution of chromatin modification to C. albicans biology is still largely unknown. For the first time, we analyzed C. albicans chromatin modifications on a genome-wide basis. We demonstrate that specific chromatin states are associated with distinct regions of the C. albicans genome and identify the roles of the chromatin modifiers Sir2 and Set1 in shaping C. albicans chromatin and gene expression.

scholarly journals Epigenetic Changes of the Cyp11a1 Promoter Region in Granulosa Cells Undergoing Luteinization During Ovulation in Female Rats

Endocrinology ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 3344-3354 ◽  
Author(s):  
Maki Okada ◽  
Lifa Lee ◽  
Ryo Maekawa ◽  
Shun Sato ◽  
Takuya Kajimura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Granulosa Cells ◽  
Chromatin Immunoprecipitation ◽  
Promoter Region ◽  
Binding Protein ◽  
Female Rats ◽  
Proximal Promoter ◽  
Lh Surge ◽  
Enhancer Binding Protein

The ovulatory LH surge induces rapid up-regulation of Cyp11a1 in granulosa cells (GCs) undergoing luteinization during ovulation. This study investigated in vivo whether epigenetic controls including histone modifications and DNA methylation in the promoter region are associated with the rapid increase of Cyp11a1 gene expression after LH surge. GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and 4 h and 12 h after human (h)CG injection. Cyp11a1 mRNA levels rapidly increased after hCG injection, reached a peak at 4 hours, and then remained elevated until 12 hours. DNA methylation status in the Cyp11a1 proximal promoter region was hypomethylated and did not change at any of the observed times after hCG injection. Chromatin immunoprecipitation assays revealed that the levels of trimethylation of lysine 4 on histone H3 (H3K4me3), an active mark for transcription, increased, whereas the levels of H3K9me3 and H3K27me3, which are marks associated with repression of transcription, decreased in the Cyp11a1 proximal promoter after hCG injection. Chromatin condensation, which was analyzed using deoxyribonuclease I, decreased in the Cyp11a1 proximal promoter after hCG injection. Chromatin immunoprecipitation assays also showed that the binding activity of CAATT/enhancer-binding protein-β to the Cyp11a1 proximal promoter increased after hCG injection. Luciferase assays revealed that the CAATT/enhancer-binding protein-β-binding site had transcriptional activity and contributed to basal and cAMP-induced Cyp11a1 expression. These results suggest that changes in histone modification and chromatin structure in the Cyp11a1 proximal promoter are involved in the rapid increase of Cyp11a1 gene expression in GCs undergoing luteinization during ovulation.

scholarly journals A Genome-Wide Chronological Study of Gene Expression and Two Histone Modifications, H3K4me3 and H3K9ac, during Developmental Leaf Senescence

2015 ◽  
Vol 168 (4) ◽  
pp. 1246-1261 ◽  
Author(s):  
Judy A. Brusslan ◽  
Giancarlo Bonora ◽  
Ana M. Rus-Canterbury ◽  
Fayha Tariq ◽  
Artur Jaroszewicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Leaf Senescence ◽  
Genome Wide ◽  
A Genome

scholarly journals Multivariable regulation of gene expression plasticity in metazoans

2019 ◽  
Author(s):  
Long Xiao ◽  
Zhiguang Zhao ◽  
Fei He ◽  
Zhuo Du
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Regulation Of Gene Expression ◽  
Rapid Change ◽  
High Plasticity ◽  
Expression Levels ◽  
Genome Wide ◽  
Expression Potential ◽  
Highly Correlated

ABSTRACTAn important capacity of genes is the rapid change of expression levels to cope with environment, known as expression plasticity. Elucidating the genomic mechanisms determining expression plasticity is critical for understanding the molecular basis of phenotypic plasticity, fitness, and adaptation. In this study, we systematically quantified genome-wide gene expression plasticity in four metazoan species by integrating changes of expression levels under a large number of genetic and environmental conditions. From this, we demonstrated that expression plasticity measures a distinct feature of gene expression that is orthogonal to other well-studies features including gene expression potential and tissue specificity/broadness. Expression plasticity is conserved across species with important physiological implications. The magnitude of expression plasticity is highly correlated with gene function and genes with high plasticity are implicated in disease susceptibility. Genome-wide analysis identified many conserved promoter cis-elements, trans-acting factors (such as CFCF), and gene body histone modifications (H3K36me3, H3K79me2, and H4K20me1) that are significantly associated with expression plasticity. Analysis of expression changes in perturbation experiments further validated a causal role of specific transcription factors and histone modifications. Collectively, this work reveals general properties, physiological implications, and multivariable regulation of gene expression plasticity in metazoans, extending the mechanistic understanding of gene regulation.

scholarly journals Sex-chromosome dosage effects on gene expression in humans

2018 ◽  
Vol 115 (28) ◽  
pp. 7398-7403 ◽  
Author(s):  
Armin Raznahan ◽  
Neelroop N. Parikshak ◽  
Vijay Chandran ◽  
Jonathan D. Blumenthal ◽  
Liv S. Clasen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Sex Chromosome ◽  
Theoretical Models ◽  
Cellular Functions ◽  
Systematic Map ◽  
Genome Expression ◽  
Dosage Effects ◽  
Genome Wide ◽  
Coexpression Networks

A fundamental question in the biology of sex differences has eluded direct study in humans: How does sex-chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex-chromosome aneuploidies (XO, XXX, XXY, XYY, and XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity among evolutionarily preserved X-Y homologs and update prevailing theoretical models for SCD compensation by detecting X-linked genes that increase expression with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex-chromosome genes regulate specific coexpression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. These gene coexpression results converge with analysis of transcription factor binding site enrichment and measures of gene expression in murine knockout models to spotlight the dosage-sensitive X-linked transcription factor ZFX as a key mediator of SCD effects on wider genome expression. Our findings characterize the effects of SCD broadly across the genome, with potential implications for human phenotypic variation.

scholarly journals Combinatorial control of diverse metabolic and physiological functions by transcriptional regulators of the yeast sulfur assimilation pathway

2012 ◽  
Vol 23 (15) ◽  
pp. 3008-3024 ◽  
Author(s):  
Allegra A. Petti ◽  
R. Scott McIsaac ◽  
Olivia Ho-Shing ◽  
Harmen J. Bussemaker ◽  
David Botstein
Keyword(s):  
Gene Expression ◽  
Redox Homeostasis ◽  
Biological Processes ◽  
Methionine Metabolism ◽  
Sulfur Assimilation ◽  
Cellular Functions ◽  
Iron Sulfur Cluster ◽  
Regulatory Circuit ◽  
Genome Wide ◽  
Combinatorial Control

Methionine abundance affects diverse cellular functions, including cell division, redox homeostasis, survival under starvation, and oxidative stress response. Regulation of the methionine biosynthetic pathway involves three DNA-binding proteins—Met31p, Met32p, and Cbf1p. We hypothesized that there exists a “division of labor” among these proteins that facilitates coordination of methionine biosynthesis with diverse biological processes. To explore combinatorial control in this regulatory circuit, we deleted CBF1, MET31, and MET32 individually and in combination in a strain lacking methionine synthase. We followed genome-wide gene expression as these strains were starved for methionine. Using a combination of bioinformatic methods, we found that these regulators control genes involved in biological processes downstream of sulfur assimilation; many of these processes had not previously been documented as methionine dependent. We also found that the different factors have overlapping but distinct functions. In particular, Met31p and Met32p are important in regulating methionine metabolism, whereas Cbf1p functions as a “generalist” transcription factor that is not specific to methionine metabolism. In addition, Met31p and Met32p appear to regulate iron–sulfur cluster biogenesis through direct and indirect mechanisms and have distinguishable target specificities. Finally, CBF1 deletion sometimes has the opposite effect on gene expression from MET31 and MET32 deletion.

scholarly journals Genome-wide Profiling of Histone Lysine Butyrylation Reveals its Role in the Positive Regulation of Gene Transcription in Rice

Rice ◽  
2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuai Liu ◽  
Guanqing Liu ◽  
Peifeng Cheng ◽  
Chao Xue ◽  
Yong Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Rice Genome ◽  
Enrichment Analysis ◽  
Carbon Chain ◽  
Main Body ◽  
Rice Varieties ◽  
Genome Wide ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Intergenic Regions

Abstract Background Histone modifications play important roles in growth and development of rice (Oryza sativa L.). Lysine butyrylation (Kbu) with a four-carbon chain is a newly-discovered histone acylation modification in rice. Main Body In this study, we performed chromatin immunoprecipitation sequencing (ChIP-seq) analyses, the result showed that major enrichment of histone Kbu located in genebody regions of rice genome, especially in exons. The enrichment level of Kbu histone modification is positively correlated with gene expression. Furthermore, we compared Kbu with DNase-seq and other histone modifications in rice. We found that 60.06% Kub enriched region co-located with DHSs in intergenic regions. The similar profiles were detected among Kbu and several acetylation modifications such as H3K4ac, H3K9ac, and H3K23ac, indicating that Kbu modification is an active signal of transcription. Genes with both histone Kbu and one other acetylation also had significantly increased expression compared with genes with only one acetylation. Gene Ontology (GO) enrichment analysis revealed that these genes with histone Kbu can regulate multiple metabolic process in different rice varieties. Conclusion Our study showed that the lysine butyrylation modificaiton may promote gene expression as histone acetylation and will provide resources for futher studies on histone Kbu and other epigenetic modifications in plants.

scholarly journals Epigenetic reprogramming of human macrophages by an intestinal pathogen

2021 ◽  
Author(s):  
Indra Bekere ◽  
Jiabin Huang ◽  
Marie Schnapp ◽  
Maren Rudolph ◽  
Laura Berneking ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Yersinia Enterocolitica ◽  
Histone Modifications ◽  
Immune Cells ◽  
Rho Gtpase ◽  
Innate Immune ◽  
Human Macrophages ◽  
Genome Wide ◽  
Molecular Patterns

AbstractVarious pathogens systematically reprogram gene expression in innate immune cells, but the underlying mechanisms are largely unknown. We investigated whether the enteropathogen Yersinia enterocolitica alters chromatin states to reprogram gene expression in primary human macrophages. Genome-wide chromatin immunoprecipitation (ChIP) seq analyses showed that pathogen-associated molecular patterns (PAMPs) induced up- or down-regulation of histone modifications (HM) at approximately 14500 loci in promoters and enhancers. Effectors of Y. enterocolitica reorganized about half of these dynamic HM, with the effector YopP being responsible for about half of these modulatory activities. The reorganized HM were associated with genes involved in immune response and metabolism. Remarkably, the altered HM also associated with 61 % of all 534 known Rho GTPase pathway genes, revealing a new level in Rho GTPase regulation and a new aspect of bacterial pathogenicity. Changes in HM were associated to varying degrees with corresponding gene expression, e. g. depending on chromatin localization and cooperation of the HM. Overall, Y. enterocolitica profoundly reorganizes HM in human macrophages to reprogram key gene expression programs of the innate immune response.Author SummaryHuman pathogenic bacteria can affect epigenetic histone modifications to modulate gene expression in host cells. However, a systems biology analysis of this bacterial virulence mechanism in immune cells has not been performed. Here we analyzed genome-wide epigenetic histone modifications and associated gene expression changes in primary human macrophages infected with enteropathogenic Yersinia enterocolitica. We demonstrate that Yersinia virulence factors extensively reprogram the histone modifications and associated gene expression triggered by the pathogen-associated molecular patterns (PAMPs) of the bacteria. The epigenetically modulated genes are involved in several key pathways of the macrophage immune response, including the Rho GTPase pathway, revealing a novel level of Rho GTPase regulation by a bacterial pathogen. Overall, our findings provide an in-depth view of epigenetic and gene expression changes during host-pathogen interaction and might have further implications for understanding of the innate immune memory in macrophages.

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