Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of Ssrp1 KO on chromatin accessibility in mouse adipose stem cells [ATAC-seq]

ABSTRACT: Preservation of nucleosomes during replication has been extensively studied, while the maintenance of nucleosomes during transcription has gotten less attention. The histone chaperone FACT is involved in transcription elongation, although whether it disassembles or assembles nucleosomes during the passage of RNA polymerase is still unclear. We deleted the FACT subunit in adult mice to clarify the function of FACT in mammals. FACT loss was lethal due to bone marrow and intestinal failure, where the earliest progenitors completely vanished, while several other cell types were increased or decreased. Using cells isolated from several tissues, we showed that FACT loss was lethal only for stem cells but not cells differentiated in vitro. FACT depletion led to increased chromatin accessibility in a transcription-dependent manner, suggesting that nucleosomes are lost from transcribed regions in the absence of FACT. The most prominent response to the loss of chromatin integrity was the activation of interferon signaling and the accumulation of immunocytes in sensitive organs. FACT maintained chromatin integrity during transcription in mammalian adult stem cells, suggesting that chromatin transcription in these cells is different from more differentiated cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE189659 | GEO | 2021/11/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Effect of Ssrp1 KO on transcriptome in mouse adipose stem cells [RNA-seq]

Project description:Preservation of nucleosomes during replication has been extensively studied, while the maintenance of nucleosomes during transcription has gotten less attention. The histone chaperone FACT is involved in transcription elongation, although whether it disassembles or assembles nucleosomes during the passage of RNA polymerase is still unclear. We deleted the FACT subunit in adult mice to clarify the function of FACT in mammals. FACT loss was lethal due to bone marrow and intestinal failure, where the earliest progenitors completely vanished, while several other cell types were increased or decreased. Using cells isolated from several tissues, we showed that FACT loss was lethal only for stem cells but not cells differentiated in vitro. FACT depletion led to increased chromatin accessibility in a transcription-dependent manner, suggesting that nucleosomes are lost from transcribed regions in the absence of FACT. The most prominent response to the loss of chromatin integrity was the activation of interferon signaling and the accumulation of immunocytes in sensitive organs. FACT maintained chromatin integrity during transcription in mammalian adult stem cells, suggesting that chromatin transcription in these cells is different from more differentiated cells.

2021-11-30 | GSE189662 | GEO

Effect of FACT depletion on the cell composition of bone marrow and intestine in mice

2021-12-02 | GSE189866 | GEO

Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells

Project description:The conserved and essential histone chaperone FACT (Facilitates Chromatin Transcription) reorganizes nucleosomes during DNA transcription, replication and repair and ensures both, efficient elongation of RNA Pol II and nucleosome integrity. In mammalian cells, FACT is a heterodimer, consisting of SSRP1 and SUPT16. Here, we show that in contrast to yeast, FACT accumulates at the transcription start site of genes reminiscent of RNA Polymerase II profile. Depletion of FACT in mouse embryonic stem cells leads to de-regulation of developmental and pro-proliferative genes concomitant with hyper-proliferation of mES cells. Using MNase-, ATAC-, and Nascent Elongating Transcript Sequencing (NET-seq) we show that up-regulation of genes coincides with loss of nucleosomes upstream of the TSS and concomitant increase in antisense transcription, indicating that FACT impacts the promoter architecture to regulate expression of these genes. Finally, we demonstrate a role for FACT in cell fate determination and show that FACT depletion primes ES cells for the neuronal lineage.

2018-06-13 | GSE90906 | GEO

FACT activity and histone H3-K56 acetylation promote optimal establishment of chromatin architecture independent of ongoing transcription in Saccharomyces cerevisiae [MNase-Seq]

Project description:FACT is a histone chaperone that can destabilize or assemble nucleosomes. Acetylation of histone H3-K56 weakens a histone:DNA contact that is central to FACT activity, suggesting that this modification could affect FACT functions. We tested this by asking how mutations of H3-K56 and FACT affect nucleosome structure, chromatin integrity, and transcription output. Mimics of unacetylated or permanently acetylated H3-K56 had different effects on FACT in vitro and in vivo as expected, but H3-K56 and FACT mutations caused surprisingly similar changes in transcription of individual genes. Notably, neither the changes in transcript levels nor the effects on nucleosome occupancy resulting from mutations conformed to the model that FACT is needed to overcome nucleosomal barriers during transcription initiation or elongation. Instead, the results suggest that both FACT and H3-K56ac are involved in establishing chromatin architecture prior to transcription and restoring it afterwards. They contribute to a process that optimizes transcription frequency, especially at conditionally expressed genes, and restores chromatin integrity after transcription, especially at the +1 nucleosome to block antisense transcription, but FACT appears to be less involved than expected in directly promoting transcription.

2019-03-06 | GSE118330 | GEO

FACT activity and histone H3-K56 acetylation promote optimal establishment of chromatin architecture independent of ongoing transcription in Saccharomyces cerevisiae [RNA-Seq]

2019-03-06 | GSE118331 | GEO

Prevention of chromatin destabilization by FACT is crucial for malignant transformation

Project description:Histone chaperone FACT is commonly expressed and essential for the viability of transformed but not normal cells and its expression levels correlate with poor prognosis in cancer patients. FACT binds several components of nucleosomes and has been viewed as a factor destabilizing nucleosomes to facilitate RNA polymerase passage. To connect FACT’s role in transcription with the viability of tumor cells, we analyzed genome-wide FACT binding to chromatin in conjunction with transcription in mouse and human cells with different degrees of FACT dependence. While genomic distribution and density of FACT correlated with the intensity of transcription, FACT knockout or knockdown was unexpectedly accompanied by the elevation, rather than suppression, of transcription and with the destabilization of chromatin. These data suggest that the real function of FACT is to stabilize and reassemble nucleosomes disturbed by transcription. This function is apparently vital for tumor cells because malignant transformation is accompanied by chromatin destabilization.

2019-06-12 | GSE132576 | GEO

Prevention of chromatin destabilization by FACT is crucial for malignant transformation [gene expression]

2019-06-14 | GSE132695 | GEO

A Role for FACT in RNA Polymerase II Promoter-Proximal Pausing

Project description:This SuperSeries is composed of the SubSeries listed below. FACT (Facilitates Chromatin Transcription) is an evolutionarily conserved histone chaperone that was initially identified as an activity capable of promoting RNA polymerase II transcription through nucleosomes in vitro. In this report, we describe a global analysis of FACT function in Pol II transcription in Drosophila. We present evidence that loss of FACT has a dramatic impact on Pol II elongation-coupled processes including H3K4 and H3K36 methylation, consistent with a role for FACT in coordinating histone modification and chromatin architecture during Pol II transcription. Importantly, we identify a role for FACT in the maintenance of promoter proximal Pol II pausing, a key step in transcription activation in higher eukaryotes. These findings bring to light a broader role for FACT in the regulation of Pol II transcription.

2019-06-14 | GSE129236 | GEO

FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner [ChIP-exo]

Project description:The histone chaperone FACT occupies transcribed regions where it plays prominent roles in maintaining chromatin integrity and preserving epigenetic information. How it is targeted to transcribed regions, however, remains unclear. Proposed models for how FACT finds its way to transcriptionally active chromatin include docking on the RNA polymerase II (RNAPII) C-terminal domain (CTD), recruitment by elongation factors, recognition of modified histone tails and binding partially disassembled nucleosomes. Here, we systematically tested these and other scenarios in Saccharomyces cerevisiae and found that FACT binds transcribed chromatin, not RNAPII. Through a combination of experimental and mathematical modeling evidence, we propose that FACT recognizes the +1 nucleosome, as it is partially unwrapped by the engaging RNAPII, and spreads to downstream nucleosomes aided by the chromatin remodeler Chd1. Our work clarifies how FACT interacts with genes, suggests a processive mechanism for FACT function, and provides a framework to further dissect the molecular mechanisms of transcription-coupled histone chaperoning.

2021-07-26 | GSE155138 | GEO

FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner [MNase-ChIP-Seq]

2021-07-26 | GSE155143 | GEO