Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromosome Compartments on the Inactive X Guide TAD Formation Independently of Transcription during X-Reactivation

ABSTRACT: To investigate the dynamics of X-chromosome reactivation, we differentiated mouse embryonic stem cells (ESCs) into neural precursor cells (NPCs) and later reprogrammed them into induced pluripotent stem cells (iPSCs). During the conversions of NPCs into iPSC, we assessed the kinetics of X-chromosome reactivation. We generated allele-specific RNA-seq datasets to assess gene reactivation dynamics, employed ATAC-seq to investigate chromatin opening dynamics and performed in situ Hi-C to explore dynamics of chromosome structure.

ORGANISM(S): Mus musculus

PROVIDER: GSE157448 | GEO | 2021/04/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation.

Project description:A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator.

| S-EPMC8190187 | biostudies-literature

Chromosome Compartments on the Inactive X Guide TAD Formation Independently of Transcription during X-Reactivation

Project description:Chromosome Compartments on the Inactive X Guide TAD Formation Independently of Transcription during X-Reactivation

| PRJNA661320 | ENA

Transcriptional dynamics of paternal X chromosome reveals different epigenetic memory of the inactive state in the inner cell mass

Project description:This study concerns the dynamics of reprogramming of the inactive X chromosome in the inner cell mass of the E3.5-4.5 mouse blastocysts. We use single cell, allele-specific transcriptomic analyses to define the precise timing of paternal X-linked gene reactivation, as well as nascent RNA FISH and immunuofluorescence to follow the loss of chromatin marks such as H3K27me3. We find evidence that different genes show very different timing of reactivation indicating an epigenetic memory of the inactive state in some cases but not in others. In exploring whether PRC2 might be part of this memory we uncover a role for the X-linked histone demethylase Utx (a gene that actually escapes XCI), in the efficiency of H3K27me3 erasure and reactivation of of the paternal X. This work describes the precise timing and potential mechanisms of X-chromosome reactivation in vivo for the first time.

2017-09-08 | GSE89900 | GEO

Genetic and epigenetic determinants of reactivation of Mecp2 and the inactive X chromosome in neural stem cells (MeD-seq)

Project description:Rett Syndrome is a neurodevelopmental disorder in girls that is caused by heterozygous inactivation of the chromatin remodeler gene MECP2. Rett Syndrome may therefore be treated by reactivation of the wild type copy of MECP2 from the inactive X chromosome. Most studies that model Mecp2 reactivation have used mouse fibroblasts rather than neural cells, which would be critical for phenotypic reversal, and rely on fluorescent reporters that lack adequate sensitivity. Here, we present a mouse model system for monitoring Mecp2 reactivation that is more sensitive and versatile than any bioluminescent and fluorescent system currently available. The model consists of neural stem cells derived from female mice with a dual reporter system where MECP2 is fused to NanoLuciferase and TdTomato on the inactive X chromosome. We show by bioluminescence and fluorescence that Mecp2 is synergistically reactivated by 5-Aza treatment and Xist knockdown. As expected, other genes on the inactive X chromosome are also reactivated, the majority of which overlaps with genes reactivated early during reprogramming of mouse embryonic fibroblasts to iPSCs. Genetic and epigenetic features such as CpG density, SINE elements, distance to escapees and CTCF binding are consistent indicators of reactivation, whereas different higher order chromatin areas are either particularly prone or resistant to reactivation. Our MeCP2 reactivation monitoring system thereby suggests that genetic and epigenetic features on the inactive X chromosome affect reactivation of its genes, irrespective of cell type or procedure of reactivation.

2022-01-24 | GSE166146 | GEO

Genetic and epigenetic determinants of reactivation of Mecp2 and the inactive X chromosome in neural stem cells (RNA-seq)

2022-01-24 | GSE166145 | GEO

Cause and consequence of tethering a sub-TAD to different nuclear compartments

Project description:Detailed genomic contact maps have revealed that chromosomes are composed of developmentally stable topologically associated domains (TADs) and more flexible sub-TADs. These domains reside in active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1 or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear sub-compartments with distinct chromatin signatures. Focal protein recruitment caused the entire sub- TAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was uncoupled from gene expression changes and enzymatically modifying histones per se was insufficient for repositioning. Collectively this suggests that transassociated factors determine three-dimensional compartmentalization independent of their cis-effect on local chromatin composition and activity. 4C-seq was performed on a range of viewpoints in 129/Sv;C57BL/6 embryonic stem cells carying a lacO array in chromosome 8 and 11.

2015-12-19 | E-GEOD-76174 | biostudies-arrayexpress

CRISPR Screen: The Interferon γ Pathway Enhances Pluripotency and X-Chromosome Reactivation in iPSC Reprogramming

Project description:To investigate the genes and pathways involved in X-chromosome reactivation and pluripotency acquisition, we generated a whole-genome CRISPR knockout screen during female NPC reprogramming into iPSCs. We analyzed the gRNA abundance in NPCs and three different reprogramming populations: non-pluripotent, early pluripotent and late pluripotent. Pair-wise comparisons of gRNA frequencies in different populations were done to identify genes and pathways involved in cell survival in reprogramming conditions, colony formation, early pluripotency acquisition and late pluripotency/X-chromosome reactivation.

2024-08-07 | GSE236244 | GEO

Cell fusion-mediated pluripotent reprogramming triggers ordered changes in chromatin and gene expression across the human inactive X chromosome

Project description:Erasure of epigenetic memory is required to convert somatic cells towards pluripotency. Reactivation of the inactive X chromosome (Xi) has been used to model epigenetic reprogramming in mouse, but human studies are hampered by Xi epigenetic instability and difficulties in tracking partially reprogrammed iPSCs. Here we used cell fusion to examine the earliest events in the reprogramming-induced Xi reactivation of human female fibroblasts. We show a rapid and widespread loss of Xi-associated H3K27me3 and XIST in fused cells that precedes the bi-allelic expression of selected Xi-genes by many heterokaryons (30-50%). After cell division, RNA-FISH and RNA-Seq analysis confirmed that Xi reactivation remained partial and showed that induction of human pluripotency-specific XACT transcripts occurred, but was rare (1%). These data effectively separate pre- and post-mitotic events in reprogramming-induced Xi reactivation, and suggest a hierarchy where early events such as XIST-delocalisation, are required but are insufficient to establish stable human X reactivation. We performed RNA-sequencing of human fibroblast clones derived from TERT-immortalised NHDF17914 (Lonza) before and at 5 days after fusion with mouse ESC (E14Tg2a:puroR). Two biological replicates were performed and sequenced.

2016-07-01 | E-GEOD-77443 | biostudies-arrayexpress

Perturbed maintenance of transcriptional repression on the inactive X-chromosome in the mouse brain after XIST deletion

Project description:The long noncoding RNA, Xist, is critical for initiation and establishment of X- chromosome inactivation during embryogenesis in mammals but it is unclear whether its continued expression is required for maintaining X inactivation in vivo. By using an inactive X chromosome-linked MeCP2-GFP reporter, which allowed us to enumerate reactivation events in the mouse brain even when they occur in very few cells, we found that deletion of Xist in the brain after establishment of X chromosome inactivation leads to reactivation in 2-5% of neurons and in a smaller fraction of astrocytes. In contrast to global loss of both H3 lysine 27 tri-methylation (H3K27m3) and histone H2A lysine 119 monoubiquitylation (H2AK119ub1) we observed upon Xist deletion, alterations in CpG methylation were subtle, and this was mirrored by only minor alterations in X- chromosome-wide gene expression levels. Our results demonstrate that Xist is required for maintaining tight transcriptional repression on the inactive X-chromosome and that partial loss of X-dosage compensation in the absence of Xist in the brain is well tolerated.

2018-08-28 | GSE119066 | GEO

Contiguous Erosion of the Inactive X in Human Pluripotency Concludes With Global DNA Hypomethylation

Project description:Female human pluripotent stem cells (hPSCs) are prone to undergoing X chromosome erosion (XCE), a progressive loss of key epigenetic features on the inactive X that initiates with repression of XIST, the long non-coding RNA required for X inactivation. As a result, previously silenced genes on the eroding X (Xe) reactivate, some of which are thought to provide selective advantages. To-date, the sporadic and progressive nature of XCE has largely obscured its scale, dynamics, and key transition events. To address this knowledge gap, we performed an integrated analysis of DNA methylation (DNAme), chromatin accessibility, and gene expression across hundreds of hPSC samples. Differential methylation across the Xe enables ordering female hPSCs across a trajectory of XCE from initiation to terminal stages. Our results identify a crucial cis-regulatory element for XIST expression, trace contiguously growing domains of reactivation to a few euchromatic origins on the Xi, and indicate that the late-stage Xe impairs DNAme genome-wide. Surprisingly, from this altered epigenetic landscape emerge select features of naïve pluripotency, suggesting its link to X chromosome dosage may be partially conserved in human embryonic development.

2021-06-15 | GSE167883 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data