scholarly journals H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction

2020 ◽  
pp. 201920725 ◽  
Author(s):  
Sean E. Healton ◽  
Hugo D. Pinto ◽  
Laxmi N. Mishra ◽  
Gregory A. Hamilton ◽  
Justin C. Wheat ◽  
...  
Keyword(s):  
Repetitive Sequence ◽  
Repetitive Sequences ◽  
Gene Activation ◽  
Embryonic Stem ◽  
Repetitive Elements ◽  
Major Satellite ◽  
Linker Histones ◽  
Chromatin Compaction ◽  
H3k9 Trimethylation

Nearly 50% of mouse and human genomes are composed of repetitive sequences. Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker histones in silencing repetitive elements in mouse embryonic stem cells. Strong H1 depletion causes a profound de-repression of several classes of repetitive sequences, including major satellite, LINE-1, and ERV. Activation of repetitive sequence transcription is accompanied by decreased H3K9 trimethylation of repetitive sequence chromatin. H1 linker histones interact directly with Suv39h1, Suv39h2, and SETDB1, the histone methyltransferases responsible for H3K9 trimethylation of chromatin within these regions, and stimulate their activity toward chromatin in vitro. However, we also implicate chromatin compaction mediated by H1 as an additional, dominant repressive mechanism for silencing of repetitive major satellite sequences. Our findings elucidate two distinct, H1-mediated pathways for silencing heterochromatin.

scholarly journals DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction

2007 ◽  
Vol 177 (3) ◽  
pp. 401-411 ◽  
Author(s):  
Nick Gilbert ◽  
Inga Thomson ◽  
Shelagh Boyle ◽  
James Allan ◽  
Bernard Ramsahoye ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure ◽  
Nuclear Organization ◽  
Chromatin Condensation ◽  
Embryonic Stem ◽  
Pericentric Heterochromatin ◽  
Epigenetic Mark ◽  
Linker Histones ◽  
Chromatin Compaction ◽  
Nucleosome Structure

DNA methylation has been implicated in chromatin condensation and nuclear organization, especially at sites of constitutive heterochromatin. How this is mediated has not been clear. In this study, using mutant mouse embryonic stem cells completely lacking in DNA methylation, we show that DNA methylation affects nuclear organization and nucleosome structure but not chromatin compaction. In the absence of DNA methylation, there is increased nuclear clustering of pericentric heterochromatin and extensive changes in primary chromatin structure. Global levels of histone H3 methylation and acetylation are altered, and there is a decrease in the mobility of linker histones. However, the compaction of both bulk chromatin and heterochromatin, as assayed by nuclease digestion and sucrose gradient sedimentation, is unaltered by the loss of DNA methylation. This study shows how the complete loss of a major epigenetic mark can have an impact on unexpected levels of chromatin structure and nuclear organization and provides evidence for a novel link between DNA methylation and linker histones in the regulation of chromatin structure.

scholarly journals Drosophila H1 Regulates the Genetic Activity of Heterochromatin by Recruitment of Su(var)3-9

Science ◽  
2013 ◽  
Vol 340 (6128) ◽  
pp. 78-81 ◽  
Author(s):  
Xingwu Lu ◽  
Sandeep N. Wontakal ◽  
Harsh Kavi ◽  
Byung Ju Kim ◽  
Paloma M. Guzzardo ◽  
...  
Keyword(s):  
Rna Interference ◽  
Small Rna ◽  
Repetitive Sequences ◽  
Histone H3 ◽  
Chromatin Compaction ◽  
Genetic Activity ◽  
Established Role ◽  
Eukaryotic Genomes

Eukaryotic genomes harbor transposable elements and other repetitive sequences that must be silenced. Small RNA interference pathways play a major role in their repression. Here, we reveal another mechanism for silencing these sequences in Drosophila. Depleting the linker histone H1 in vivo leads to strong activation of these elements. H1-mediated silencing occurs in combination with the heterochromatin-specific histone H3 lysine 9 methyltransferase Su(var)3-9. H1 physically interacts with Su(var)3-9 and recruits it to chromatin in vitro, which promotes H3 methylation. We propose that H1 plays a key role in silencing by tethering Su(var)3-9 to heterochromatin. The tethering function of H1 adds to its established role as a regulator of chromatin compaction and accessibility.

scholarly journals A Central Role for Canonical PRC1 in Shaping the 3D Nuclear Landscape

2019 ◽  
Author(s):  
Shelagh Boyle ◽  
Ilya M. Flyamer ◽  
Iain Williamson ◽  
Dipta Sengupta ◽  
Wendy A. Bickmore ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Gene Activation ◽  
Embryonic Stem ◽  
Nuclear Architecture ◽  
Regulatory System ◽  
Spatial Arrangement ◽  
Polycomb Group ◽  
List Type

AbstractPolycomb group (PcG) proteins silence gene expression by chemically and physically modifying chromatin. A subset of PcG target loci are compacted and cluster in the nucleus to form observable bodies; a conformation which is thought to contribute to gene silencing. However, how these interactions influence gross nuclear organisation and their relationship with transcription remains poorly understood. Here we examine the role of Polycomb Repressive Complex 1 (PRC1) in shaping 3D genome organization in mouse embryonic stem cells (mESCs). Using a combination of imaging and Hi-C analyses we show that PRC1-mediated long-range interactions are independent of CTCF and can bridge sites at a megabase scale. Impairment of PRC1 enzymatic activity does not directly disrupt these interactions. We demonstrate that PcG targets coalesce in vivo, and that developmentally induced expression of one of the target loci disrupts this spatial arrangement. Finally, we show that transcriptional activation and the loss of PRC1-mediated interactions are seperable events. These findings provide important insights into the function of PRC1, whilst highlighting the complexity of this regulatory system.HighlightsLoss of RING1B substantially disrupts nuclear architecture.PRC1 mediated looping can occur at a Mb scale and is independent of CTCF.Polycomb mediated looping is driven by canonical PRC1 complexes.Multimeric PRC1-mediated interactions occur in vitro and in vivo.Disruption of PRC1-mediated looping is independent of gene activation.

scholarly journals Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells

2020 ◽  
Author(s):  
Clara Lopes Novo ◽  
Emily Wong ◽  
Colin Hockings ◽  
Chetan Poudel ◽  
Eleanor Sheekey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Phase Separation ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Satellite Repeat ◽  
Static State ◽  
Major Satellite ◽  
Nuclear Domains

SummaryHeterochromatin maintains genome integrity and function, and is organised into distinct nuclear domains. Some of these domains are proposed to form by phase separation through the accumulation of HP1α. Mammalian heterochromatin contains noncoding major satellite repeats (MSR), which are highly transcribed in mouse embryonic stem cells (ESCs). Here, we report that MSR transcripts can drive the formation of HP1α droplets in vitro, and scaffold heterochromatin into dynamic condensates in ESCs, leading to the formation of large nuclear domains that are characteristic of pluripotent cells. Depleting MSR transcripts causes heterochromatin to transition into a more compact and static state. Unexpectedly, changing heterochromatin’s biophysical properties has severe consequences for ESCs, including chromosome instability and mitotic defects. These findings uncover an essential role for MSR transcripts in modulating the organisation and properties of heterochromatin to preserve genome stability. They also provide new insights into the processes that could regulate phase separation and the functional consequences of disrupting the properties of heterochromatin condensates.

Controlling the in vitro differentiation of embryonic stem cells for myocardial tissue engineering applications

2009 ◽  
Author(s):  
Dong-Bo Ou ◽  
Rui Chen ◽  
Xiong-Tao Liu ◽  
Jing-Jing Guo ◽  
Hong-Tao Wang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Myocardial Tissue ◽  
In Vitro Differentiation ◽  
Engineering Applications ◽  
Myocardial Tissue Engineering

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

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