Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of the NSL complex by TAF4A is critical for genome stability and quiescence of skeletal muscle stem cells

ABSTRACT: Acetylation of lamin A/C by the NSL complex, containing MOF and KANSL2, is instrumental for maintaining nuclear architecture and genome stability, but the mechanisms controlling expression of NSL complex components in different cell types are poorly characterized. Here, we describe that TAF4A, primarily known as a subunit of the general transcription factor TFIID, is critical for cell type-specific regulation of Kansl2 in MuSCs. Inactivation of Taf4a in MuSCs reduces expression of Kansl2 and alters post-translational modification of lamin A/C, thereby decreasing the stiffness of MuSC nuclei and disrupting the nuclear architecture. Using CUT&RUN technique, we found that TAF4A together with the heterotrimeric transcription factor NF-Y controls Kansl2 expression. In addition to destabilization of the nuclear architecture, reduced expression of Kansl2 in Taf4a-mutant MuSCs changes expression of numerous genes involved in chromatin regulation. The subsequent loss of heterochromatin and MuSC activation, in combination with pronounced genomic instability, activates MuSCs and impairs MuSC proliferation, which depletes the stem cell pool and abolishes skeletal muscle regeneration. We conclude that TAF4A-NF-Y-dependent transcription regulation safeguards heterochromatin and genome stability of MuSCs via the NSL complex.

ORGANISM(S): Mus musculus

PROVIDER: GSE299832 | GEO | 2025/09/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Regulation of the NSL complex by TAF4A is critical for genome stability and quiescence of skeletal muscle stem cells [CnR of TAF4A in WT MuSCs]

Project description:Acetylation of lamin A/C by the NSL complex, containing MOF and KANSL2, is instrumental for maintaining nuclear architecture and genome stability, but the mechanisms controlling expression of NSL complex components in different cell types are poorly characterized. Here, we describe that TAF4A, primarily known as a subunit of the general transcription factor TFIID, is critical for cell type-specific regulation of Kansl2 in MuSCs. Inactivation of Taf4a in MuSCs reduces expression of Kansl2 and alters post-translational modification of lamin A/C, thereby decreasing the stiffness of MuSC nuclei and disrupting the nuclear architecture. Using CUT&RUN technique, we found that TAF4A together with the heterotrimeric transcription factor NF-Y controls Kansl2 expression. In addition to destabilization of the nuclear architecture, reduced expression of Kansl2 in Taf4a-mutant MuSCs changes expression of numerous genes involved in chromatin regulation. The subsequent loss of heterochromatin and MuSC activation, in combination with pronounced genomic instability, activates MuSCs and impairs MuSC proliferation, which depletes the stem cell pool and abolishes skeletal muscle regeneration. We conclude that TAF4A-NF-Y-dependent transcription regulation safeguards heterochromatin and genome stability of MuSCs via the NSL complex.

2025-09-02 | GSE277867 | GEO

Regulation of the NSL complex by TAF4A is critical for genome stability and quiescence of skeletal muscle stem cells [CnR of KANSL2 in WT MuSCs]

2025-09-02 | GSE277868 | GEO

Regulation of the NSL complex by TAF4A is critical for genome stability and quiescence of skeletal muscle stem cells [CnR of NF-YA in WT MuSCs]

2025-09-02 | GSE277869 | GEO

Regulation of the NSL complex by TAF4A is critical for genome stability and quiescence of skeletal muscle stem cells [RNA-seq of MuSCs from control and Taf4asKOmice]

2025-09-02 | GSE277871 | GEO

Regulation of the NSL complex by TAF4A is critical for genome stability and quiescence of skeletal muscle stem cells [CnR of NF-YA in WT and Taf4asKO MuSCs]

2025-09-02 | GSE277870 | GEO

Kansl2 dependent acetylome study in primary Kansl2 (fl/fl) murine embryonic fibroblasts

Project description:As one of the most important post-translational protein modifications, lysine acetylation is catalyzed by lysine acetyltransferases (KATs), which catalyze the covalent attachment of an acetyl group to the N epsilon–residue of lysine. The histone acetyltransferase MOF, which represents the main histone H4 lysine-16 specific acetyltransferase, is the KAT subunit of two mutually exclusive multiprotein complexes in metazoa, namely the MSL (male-specific lethal) and the NSL (non-specific lethal) complex. Depletion of both, MOF and the NSL complex subunit Kansl2 result in selective changes of the cellular acetylome. As a consequence, modulation of nuclear lamin lysine acetylations correlate with profound changes in nuclear morphology, like micronuclei formation.

2023-01-05 | PXD038521 | Pride

The NSL complex subunit KANSL2 regulates cell stemness and tumorigenesis in glioblastoma

Project description:The NSL (nonspecific lethal) complex proteins involved in acetyltransferase activity on histones play important role during the epigenetic and transcription regulation. The KANSL2/NSL2 is an integral component of NSL and expressed in embryonic cells. We engaged to characterize KANSL2 ( protein component subunit of the KAT-8 associated nonspecific lethal complex) functions, using glioblastoma, which contains heterogenous aggressive neoplastic stem-like cells involved in tumor resistance and recurrence.

2017-02-05 | E-MTAB-4455 | biostudies-arrayexpress

Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist [RNA-seq]

Project description:Skeletal muscle possesses remarkable regenerative ability owing to the resident muscle stem cells (MuSCs). A prominent feature of quiescent MuSCs is a high content of heterochromatin. However, little is known about the mechanisms by which heterochromatin is maintained in MuSCs. We found that the mammalian Hairless (Hr) gene is expressed in quiescent MuSCs. Using a mouse model in which Hr can be specifically ablated in MuSCs, we demonstrate that Hr expression is critical for MuSC function and muscle regeneration. We show that Hr is a histone demethylase antagonist that preserves Histone 3 Lysine 9 trimethylation (H3K9me3) and maintains heterochromatin structure. Loss of Hr results in reduced H3K9me3 levels, reduced heterochromatin, increased susceptibility of MuSCs to genotoxic stress, and the accumulation of DNA damage. Our study not only elucidates the molecular mechanism by which Hr regulates histone demethylases, but also demonstrates the importance of heterochromatin maintenance in stem cell function.

2021-09-09 | GSE132189 | GEO

Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist (ChIPseq, ATACseq)

2021-09-09 | GSE132220 | GEO

Autonomous extracellular matrix remodeling controls a progressive adaptation in muscle stem cell regenerative capacity during development

Project description:Muscle stem cells (MuSC) exhibit distinct behaviors during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here we show that fetal MuSC resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. Following transplantation, fetal MuSC more efficiently expand and contribute to muscle repair. Conversely, the efficiency of niche colonization increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed in fetal MuSC, including tenascin-C, fibronectin and collagen VI. Loss-of-function experiments confirmed their essential and stage-specific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSC change the way in which they remodel their microenvironment to direct stem cell behavior in support of the unique demands of muscle development or repair. MuSCs were isolated through fluorescent-activate cell sorting usinf alpha7-integirn and CD34 as markers to identify the cell population. Total mRNA was then isolated, and samples at different developmental times were compared.

2016-01-20 | E-GEOD-76989 | biostudies-arrayexpress

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