Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells.

ABSTRACT: Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs). BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate. Moreover, genome-wide analysis of DNA accessibility following genetic or chemical inhibition, suggests a role for BPTF in maintaining the open chromatin landscape at enhancers regions in MECs. Collectively, our study implicates BPTF in maintaining the unique epigenetic state of MaSCs.

SUBMITTER: Frey WD

PROVIDER: S-EPMC5783326 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells.

Frey Wesley D WD Chaudhry Anisha A Slepicka Priscila F PF Ouellette Adam M AM Kirberger Steven E SE Pomerantz William C K WCK Hannon Gregory J GJ Dos Santos Camila O CO

Stem cell reports 20170601 1

Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs). BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with ...[more]

PMID: 28579392

Similar Datasets

Bptf maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-06-13 | GSE98004 | GEO

Bptf maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells [ChIP-Seq]

Project description:Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here we show that Bptf, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of epithelial cells in the mammary gland. Bptf depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate. Moreover, genome-wide analysis of DNA accessibility following genetic and chemical inhibition of Bptf, suggests a role for this factor in maintaining the open chromatin landscape of cis-regulatory elements in mammary epithelial cells (MECs). Collectively, our study implicates Bptf in maintaining the unique epigenetic state of MaSCs.

2017-06-13 | GSE98002 | GEO

Bptf maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells [RNA-Seq]

2017-06-13 | GSE98003 | GEO

Bptf maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells [ATAC-Seq]

2017-06-13 | GSE98001 | GEO

Bptf maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells

Project description:Bptf maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells

| PRJNA383646 | ENA

MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells.

Project description:The structurally related MAPK-activated protein kinases (MAPKAPKs or MKs) MK2, MK3 and MK5 are involved in multiple cellular functions, including cell-cycle control and cellular differentiation. Here, we show that after deregulation of cell-cycle progression, haematopoietic stem cells (HSCs) in MK2-deficient mice are reduced in number and show an impaired ability for competitive repopulation in vivo. To understand the underlying molecular mechanism, we dissected the role of MK2 in association with the polycomb group complex (PcG) and generated a MK2 mutant, which is no longer able to bind to PcG. The reduced ability for repopulation is rescued by re-introduction of MK2, but not by the Edr2-non-binding mutant of MK2. Thus, MK2 emerges as a regulator of HSC homeostasis, which could act through chromatin remodelling by the PcG complex.

| S-EPMC2688528 | biostudies-literature

Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability.

Project description:Chromodomain helicase DNA-binding domain 2 (CHD2) is a chromatin remodeling factor involved in many developmental processes. However, its role in male germ cell development has not been elucidated. Here, we confirm that CHD2 expression is enriched in the male germline. In a heterozygous knockout mouse model of Chd2 (Chd2 +/-), we demonstrated that Chd2 haploinsufficiency resulted in testicular developmental delay, an increased rate of abnormal sperm, and impaired fertility in mice. In vitro experiments in mouse spermatogonia showed that CHD2 knockdown inhibits spermatogonial self-renewal. Mechanistically, CHD2 maintains the enrichment of H3K4me3 in the Ccnb1 and Ccnd2 promotors, consequently promoting the transcription of Ccnb1 and Ccnd2. In addition, CHD2 interacts with the cleavage stimulation factor CSTF3 and upregulates the expression of OCT4 and PLZF by improving mRNA stability. This is the first study to reveal the role and mechanism of CHD2 in maintaining spermatogonial self-renewal.

| S-EPMC9700024 | biostudies-literature

myc maintains embryonic stem cell pluripotency and self-renewal.

Project description:While endogenous Myc (c-myc) and Mycn (N-myc) have been reported to be separately dispensable for murine embryonic stem cell (mESC) function, myc greatly enhances induced pluripotent stem (iPS) cell formation and overexpressed c-myc confers LIF-independence upon mESC. To address the role of myc genes in ESC and in pluripotency generally, we conditionally knocked out both c- and N-myc using myc doubly homozygously floxed mESC lines (cDKO). Both lines of myc cDKO mESC exhibited severely disrupted self-renewal, pluripotency, and survival along with enhanced differentiation. Chimeric embryos injected with DKO mESC most often completely failed to develop or in rare cases survived but with severe defects. The essential nature of myc for self-renewal and pluripotency is at least in part mediated through orchestrating pluripotency-related cell cycle and metabolic programs. This study demonstrates that endogenous myc genes are essential for mESC pluripotency and self-renewal as well as providing the first evidence that myc genes are required for early embryogenesis, suggesting potential mechanisms of myc contribution to iPS cell formation.

| S-EPMC2916696 | biostudies-literature

REST maintains self-renewal and pluripotency of embryonic stem cells.

Project description:The neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells, but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells. Heterozygous deletion of Rest (Rest+/-) and its short-interfering-RNA-mediated knockdown in mouse ES cells cause a loss of self-renewal-even when these cells are grown under self-renewal conditions-and lead to the expression of markers specific for multiple lineages. Conversely, exogenously added REST maintains self-renewal in mouse EB cells. Furthermore, Rest+/- mouse ES cells cultured under self-renewal conditions express substantially reduced levels of several self-renewal regulators, including Oct4 (also called Pou5f1), Nanog, Sox2 and c-Myc, and exogenously added REST in mouse EB cells maintains the self-renewal phenotypes and expression of these self-renewal regulators. We also show that in mouse ES cells, REST is bound to the gene chromatin of a set of miRNAs that potentially target self-renewal genes. Whereas mouse ES cells and mouse EB cells containing exogenously added REST express lower levels of these miRNAs, EB cells, Rest+/- ES cells and ES cells treated with short interfering RNA targeting Rest express higher levels of these miRNAs. At least one of these REST-regulated miRNAs, miR-21, specifically suppresses the self-renewal of mouse ES cells, corresponding to the decreased expression of Oct4, Nanog, Sox2 and c-Myc. Thus, REST is a newly discovered element of the interconnected regulatory network that maintains the self-renewal and pluripotency of mouse ES cells.

| S-EPMC2830094 | biostudies-literature

Dynamics of chromatin accessibility during TGF-?-induced EMT of Ras-transformed mammary gland epithelial cells.

Project description:Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor (TGF)-? and facilitates tumor progression. We here performed global mapping of accessible chromatin in the mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) using formaldehyde-assisted isolation of regulatory element (FAIRE)-sequencing. TGF-? and Ras altered chromatin accessibility either cooperatively or independently, and AP1, ETS, and RUNX binding motifs were enriched in the accessible chromatin regions of EpH4 and EpRas cells. Etv4, an ETS family oncogenic transcription factor, was strongly expressed and bound to more than one-third of the accessible chromatin regions in EpRas cells treated with TGF-?. While knockdown of Etv4 and another ETS family member Etv5 showed limited effects on the decrease in the E-cadherin abundance and stress fiber formation by TGF-?, gene ontology analysis showed that genes encoding extracellular proteins were most strongly down-regulated by Etv4 and Etv5 siRNAs. Accordingly, TGF-?-induced expression of Mmp13 and cell invasiveness were suppressed by Etv4 and Etv5 siRNAs, which were accompanied by the reduced chromatin accessibility at an enhancer region of Mmp13 gene. These findings suggest a mechanism of transcriptional regulation during Ras- and TGF-?-induced EMT that involves alterations of accessible chromatin, which are partly regulated by Etv4 and Etv5.

| S-EPMC5430828 | biostudies-literature

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