Kisspeptin Induces Dynamic Chromatin Modifications to Control GnRH Gene Expression

2015 ◽  
Vol 53 (5) ◽  
pp. 3315-3325 ◽  
Author(s):  
H. J. Novaira ◽  
M. L. Sonko ◽  
S. Radovick
Keyword(s):  
Gene Expression ◽  
Chromatin Modifications

Multiple chromatin modifications important for gene expression changes in cardiac hypertrophy

2006 ◽  
Vol 34 (6) ◽  
pp. 1138-1140 ◽  
Author(s):  
A.J. Bingham ◽  
L. Ooi ◽  
I.C. Wood
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Transcription Factor ◽  
Cardiac Hypertrophy ◽  
Heart Development ◽  
Adaptive Response ◽  
Chromatin Modifications ◽  
Foetal Heart ◽  
Expression Of Genes ◽  
Repressor Element

Cardiac hypertrophy is an increase in the size of cardiac myocytes to generate increased muscle mass, usually driven by increased workload for the heart. Although important during postnatal development and an adaptive response to physical exercise, excessive hypertrophy can result in heart failure. One characteristic of hypertrophy is the re-expression of genes that are normally only expressed during foetal heart development. Although the involvement of these changes in gene expression in hypertrophy has been known for some years, the mechanisms involved in this re-expression are only now being elucidated and the transcription factor REST (repressor element 1-silencing transcription factor) has been identified as an important repressor of hypertrophic gene expression.

scholarly journals DNA Methylation Patterns Expose Variations in Enhancer-Chromatin Modifications during Embryonic Stem Cell Differentiation

2020 ◽  
Author(s):  
Adi Alajem ◽  
Hava Roth ◽  
Sofia Ratgauzer ◽  
Danny Bavli ◽  
Alex Motzik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Genomic Region ◽  
Cellular Heterogeneity ◽  
Embryonic Stem Cell Differentiation ◽  
Chromatin Modifications

AbstractIn mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1-versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.Author summaryCellular dynamics are underlined by numerous regulatory layers. The regulatory mechanism of interest in this work are enhancers. Enhancers are regulatory regions responsible, mainly, for increasing the possibility of transcription of a certain gene. Enhancers are marked by two distinct chemical groups-H3K4me1 and H3K27ac on the tail of histones. Histones are the proteins responsible for DNA packaging into condensed chromatin structure. In contrast, DNA methylation is a chemical modification often found on enhancers, and is traditionally associated with repression. A long debated question revolves around the functional relevance of DNA methylation in the context of enhancers. Here, we combined the two regulatory layers, histone marks and DNA methylation, to a single measurement that can highlight DNA methylation separately on each histone mark but at the same genomic region. When isolated with H3K4me1, enhancers showed higher levels of methylation compared to H3K27ac. As we measured the same genomic locations, we show that differences of DNA methylation between these marks can only be explained by cellular heterogeneity. We also demonstrated that these enhancers tend to play roles in stem cell differentiation and expression levels of the genes they control correlate with cell-to-cell variation.

3 HISTONE H4 ACETYLATION AT LYSINE 12 AND Cdc2a EXPRESSION ARE DECREASED IN AGED MOUSE GERMINAL VESICLE-STAGE OOCYTES

2007 ◽  
Vol 19 (1) ◽  
pp. 120
Author(s):  
I. Manosalva ◽  
C. Goday ◽  
P. Esponda
Keyword(s):  
Gene Expression ◽  
Oocyte Maturation ◽  
Germinal Vesicle ◽  
Aged Mouse ◽  
Mrna Levels ◽  
Chromatin Modifications ◽  
Histone H4 ◽  
Histone H4 Acetylation ◽  
Mammalian Female ◽  
Old Mice

Ageing is a phenomenon related to mammalian female infertility. One cause of ageing-induced infertility is the abnormal meiotic maturation from germinal vesicle stage oocytes (GVs). GVs are immature oocytes, which stay arrested in the ovaries during the life span. The abnormal oocyte maturation in aged animals is partially originated from molecular changes, not well defined, such as chromatin modifications and differential gene expression. Here, we analyze chromatin modifications such as histone acetylation and the corresponding gene expression changes induced by ageing in mouse GVs. We measured by immunofluorescence histone H4 acetylation at lysine residues 5 (H4-K5), 8 (H4-K8), and 12 (H4-K12) in GVs collected from young (1 month old) and aged (12–18 months old) CDC1 female mice. Immunofluorescence was analyzed with a microscope (Leica TCS SP2 AOBS) and its image analysis software. Whereas H4-K5 and H4-K8 show similar acetylation levels in both young and old mice, significant lower acetylation of H4-K12 is detected in GVs from old mice. Since H4-K12 acetylation has been related to Cdc2a expression during oocyte maturation (Akiyama et al. 2004 Mol. Reprod. Dev. 69, 222–227; Minuzzo et al. 2005 Mol. Pharmacol. 68, 1496–1503), we investigated whether Cdc2a mRNA levels change in aged mice. Cdc2a expression was measured by RT-PCR and quantified with a densitometer (BioRad GS800). We observed a decrease of Cdc2a expression in GVs of old mice. This result is further confirmed by an immunofluorescence analysis where lower levels of Cdc2a protein in old mouse GVs was observed. In conclusion, we find that the levels of H4-K12 acetylation and Cdc2a mRNA are lower in old compared to young mouse GVs. Our observations suggest that ageing affects histone modifications such as H4-K12, which might induce chromatin remodelling and gene expression changes like that of Cdc2a.

scholarly journals Chromatin modifications remodel cardiac gene expression

2014 ◽  
Vol 103 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Prabhu Mathiyalagan ◽  
Samuel T. Keating ◽  
Xiao-Jun Du ◽  
Assam El-Osta
Keyword(s):  
Gene Expression ◽  
Chromatin Modifications ◽  
Cardiac Gene Expression ◽  
Cardiac Gene

scholarly journals DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009498
Author(s):  
Adi Alajem ◽  
Hava Roth ◽  
Sofia Ratgauzer ◽  
Danny Bavli ◽  
Alex Motzik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Genomic Region ◽  
Embryonic Stem Cell Differentiation ◽  
Chromatin Modifications

In mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H13K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1- versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.

scholarly journals Dynamic Chromatin Modifications Control GnRH Gene Expression during Neuronal Differentiation and Protein Kinase C Signal Transduction

2011 ◽  
Vol 32 (1) ◽  
pp. 154-154
Author(s):  
Anita K. Iyer ◽  
Melissa J. Brayman ◽  
Pamela L. Mellon
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Neuronal Cells ◽  
Chromatin Modifications ◽  
Rna Transcription ◽  
Enhancer Rna ◽  
Kinase C ◽  
H3 Acetylation ◽  
Pkc Activation

Abstract GnRH, a neuropeptide produced by rare, specialized hypothalamic secretory neurons, is critical for reproduction. During development, GnRH gene expression increases as neurons migrate from the olfactory placode to the hypothalamus, with highest levels in the mature, postmitotic state. While neuronal differentiation is known to be controlled by chromatin modulations, the role of chromatin dynamics in GnRH gene regulation has not been studied. Here, we use mature and immature GnRH neuronal cell models to show that both neuron-specific and protein kinase C regulation of GnRH expression are mediated by chromatin structure and histone modifications. Only in GT1-7 mature GnRH neuronal cells did GnRH regulatory elements display high sensitivity to DNase and enrichment of active histone markers histone-H3 acetylation and H3 lysine 4 trimethylation (H3K4-Me3), as well as RNA Polymerase II (RNAPII) binding and enhancer RNA transcription. In contrast, H3K9-Me2, a marker of inactive chromatin, was highest in nonneuronal cells, low in GT1-7 cells, and intermediate in immature GnRH neuronal cells. The chromatin of the GnRH gene was therefore active in mature GnRH neuronal cells, inactive in nonneuronal cells, but not fully inactive in immature GnRH neuronal cells. Activation of protein kinase C (PKC) potently represses GnRH expression. PKC activation caused closing of the chromatin and decreased RNAPII occupancy at the GnRH minimal promoter (−278/−97). At GnRH-Enhancer-1 (−2404/−2100), PKC activation decreased phosphorylated-RNAPII binding, enhancer RNA transcription, and H3 acetylation, and reciprocally increased H3K9-Me2. Chromatin modifications therefore participate in the dynamic regulation and specification of GnRH expression to differentiated hypothalamic neurons.

scholarly journals Inflammation, HIF-1, and the Epigenetics That Follows

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Claudio Brigati ◽  
Barbara Banelli ◽  
Angela di Vinci ◽  
Ida Casciano ◽  
Giorgio Allemanni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Modifications ◽  
Histone Demethylases ◽  
Chromatin Configuration ◽  
Cellular Phenotypes ◽  
The Relationship

We summarize recent findings linking inflammatory hypoxia to chromatin modifications, in particular to repressive histone signatures. We focus on the role of Hypoxia-Induced Factor-1 in promoting the activity of specific histone demethylases thus deeply modifying chromatin configuration. The consequences of these changes are depicted in terms of gene expression and cellular phenotypes. We finally integrate available data to introduce novel speculations on the relationship between inflammation, histones, and DNA function and integrity.

scholarly journals Metabolic regulation of chromatin modifications and gene expression

2018 ◽  
Vol 217 (7) ◽  
pp. 2247-2259 ◽  
Author(s):  
Juan Manuel Schvartzman ◽  
Craig B. Thompson ◽  
Lydia W.S. Finley
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Metabolic Regulation ◽  
Regulation Of Gene Expression ◽  
Enzymatic Reaction ◽  
Chromatin Modifications ◽  
Dynamic Regulation ◽  
Local Conditions ◽  
Control Of Gene Expression ◽  
Cell Fate Decisions

Dynamic regulation of gene expression in response to changing local conditions is critical for the survival of all organisms. In metazoans, coherent regulation of gene expression programs underlies the development of functionally distinct cell lineages. The cooperation between transcription factors and the chromatin landscape enables precise control of gene expression in response to cell-intrinsic and cell-extrinsic signals. Many of the chemical modifications that decorate DNA and histones are adducts derived from intermediates of cellular metabolic pathways. In addition, several of the enzymes that can remove these marks use metabolites as part of their enzymatic reaction. These observations have led to the hypothesis that fluctuations in metabolite levels influence the deposition and removal of chromatin modifications. In this review, we consider the emerging evidence that cellular metabolic activity contributes to gene expression and cell fate decisions through metabolite-dependent effects on chromatin organization.

Chromatin Signature and Transcription Factor Binding Provide a Predictive Basis for Understanding Plant Gene Expression

2019 ◽  
Vol 60 (7) ◽  
pp. 1471-1486 ◽  
Author(s):  
Zefeng Wu ◽  
Jing Tang ◽  
Junjie Zhuo ◽  
Yuhan Tian ◽  
Feiyang Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Histone Modifications ◽  
Gene Expression Level ◽  
Expression Level ◽  
Good Prediction ◽  
Chromatin Modifications ◽  
Chromatin Signature ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Chromatin accessibility and post-transcriptional histone modifications play important roles in gene expression regulation. However, little is known about the joint effect of multiple chromatin modifications on the gene expression level in plants, despite that the regulatory roles of individual histone marks such as H3K4me3 in gene expression have been well-documented. By using machine-learning methods, we systematically performed gene expression level prediction based on multiple chromatin modifications data in Arabidopsis and rice. We found that as few as four histone modifications were sufficient to yield good prediction performance, and H3K4me3 and H3K36me3 being the top two predictors with known functions related to transcriptional initiation and elongation, respectively. We demonstrated that the predictive powers differed between protein-coding and non-coding genes as well as between CpG-enriched and CpG-depleted genes. We also showed that the predictive model trained in one tissue or species could be applied to another tissue or species, suggesting shared underlying mechanisms. More interestingly, the gene expression levels of conserved orthologs are easier to predict than the species-specific genes. In addition, chromatin state of distal enhancers was moderately correlated to gene expression but was dispensable if given the chromatin features of the proximal regions of genes. We further extended the analysis to transcription factor (TF) binding data. Strikingly, the combinatorial effects of only a few TFs were roughly fit to gene expression levels in Arabidopsis. Overall, by using quantitative modeling, we provide a comprehensive and unbiased perspective on the epigenetic and TF-mediated regulation of gene expression in plants.

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