Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ATAC-sequencing data of THP-1 cells after the knockout of MSL1

ABSTRACT: Histone acetylation is associated with open chromatin and transcriptionally active genes. Specifically, acetylation of lysine 16 on histone H4 (H4K16ac) has been shown to prevent the assembly of nucleosomal arrays in vitro. This modification is catalyzed by the MYST-family histone acetyltransferase KAT8 (also known as MOF and MYST1), which is part of two distinct chromatin-associated complexes, NSL and MSL. While extensively studied in Drosophila, the functions of H4K16ac and the two KAT8-containing complexes in mammalian cells are not well understood. Here, we demonstrate a surprising complex-dependent activity of KAT8. We found that KAT8 catalyzes H4K5 and H4K8 acetylation as part of the NSL complex, whereas it catalyzes the bulk of H4K16 acetylation as part of the MSL complex. Furthermore, we show that the core proteins of the MSL complex and H4K16ac are not required for cell proliferation and global chromatin accessibility, whereas the NSL complex is essential for cell survival, as it is enriched at the promoters of housekeeping genes and is required for their transcription initiation. In summary, we show that KAT8 switches its catalytic activity and function depending on its associated proteins, and that it, as part of the NSL complex, catalyzes H4K5 and H4K8 acetylation required for the expression of genes essential for cell survival.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157583 | GEO | 2021/02/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcriptional regulation and cellular homeostasis [histone dataset]

Project description:Histone acetylation is associated with open chromatin and transcriptionally active genes. Specifically, acetylation of lysine 16 on histone H4 (H4K16ac) has been shown to prevent the assembly of nucleosomal arrays in vitro. This modification is catalyzed by the MYST-family histone acetyltransferase KAT8 (also known as MOF and MYST1), which is part of two distinct chromatin-associated complexes: NSL and MSL. While extensively studied in Drosophila, the functions of H4K16ac and the two KAT8-containing complexes in mammalian cells are not well understood. Here, we demonstrate a surprising complex-dependent activity of KAT8. We found that KAT8 catalyzes H4K5 and H4K8 acetylation as part of the NSL complex, whereas it catalyzes the bulk of H4K16 acetylation as part of the MSL complex. Furthermore, we show that the core proteins of the MSL complex and H4K16ac are not required for cell proliferation and global chromatin accessibility, whereas the NSL complex is essential for cell survival, as it is enriched at the promoters of housekeeping genes and is required for their transcription initiation. In summary, we show that KAT8 switches catalytic activity and function depending on its associated proteins, and that, as part of the NSL complex, it catalyzes H4K5 and H4K8 acetylation required for the expression of genes essential for cell survival

2021-06-29 | PXD021943 | Pride

Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcriptional regulation and cellular homeostasis [AP-MS]

2021-06-29 | PXD022267 | Pride

Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcriptional regulation and cellular homeostasis [TMT11plex whole proteome analysis]

2021-06-29 | PXD023865 | Pride

Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcriptional regulation and cellular homeostasis (ChIP-sequecing data)

2021-02-28 | GSE158736 | GEO

RNA-sequencing data of THP-1 cells after the knockdown of KANSL2, KANSL3 or KAT8

2021-02-28 | GSE158521 | GEO

Analysis of histone modification with the deletion of components of the NSL complex

Project description:The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase complex consists of 9 subunits can acetylate histone H4K16, H4K5 and H4K8. It has been known that this complex shares WDR5 subunit with the MLL/SET histone methyltransferases, suggesting that NSL complex is essential for the multiple transcriptional regulation mechanisms. However, there are few reports on the function of NSL HAT in genome, It is necessary to clarify the details and specificity of histone H4 acetylation cooperates with H3K4 methylation to regulate gene transcription. In this work, Our results show that The NSL complex plays a critical role in regulating multiple histone modifications by using the CRISPR/Cas9 NSL3-KO 293T cell line and ChIP-Seq approach. The global levels of highly enriched H4K16ac, H4K5ac, H3K4me2 and H3K4me3 at TSSs (TSS ± 3 kb region) are inhibited by NSL3-KO. NSL3-KO seemed to have little effect on the enhancer mark H3K27ac and repressor mark H3K27me3, but H3K4me1 was greatly affected by NSL3-KO. Moreover, the NSL complex govern gene transcription and identified genes by a coordinative mode of H4K16ac and H3K4me2/me3. What’s more, De novo motif analysis of MOF and NSL3 targets indicated that the NSL complex forms a gene regulatory network with multiple transcription factors by regulating their genes expression or cooperating with some factors through binding to specific motif.

2022-03-18 | GSE198645 | GEO

De novo mutations of MSL3 cause a novel X-linked syndrome due to impaired histone H4 lysine 16 acetylation

Project description:Epigenetic regulation by histone acetylation plays a key role in cellular homeostasis and its misregulation is associated with human disease. Histone 4 Lysine 16 acetylation (H4K16ac) serves a unique role amongst the many histone modifications as it directly affects chromatin structure1. The Male Specific Lethal (MSL) complex associated MOF/KAT8 histone acetyl transferase is responsible for bulk H4K16ac in flies and mammals. Yet, its importance during human development and a potential involvement in human pathologies remains largely unknown. Here, we uncover that pathogenic variants in MSL3, a component of the MSL complex, are causative for a new recognizable X-linked syndrome affecting Histone 4 Lysine 16 acetylation (H4K16ac) in both male and female individuals. Common clinical features of the syndrome include global developmental delay comprising profound speech delay, delayed ability to walk and craniofacial dysmorphism. Using patient-derived primary fibroblasts, we demonstrate that de novo variants or deletions of MSL3 affect the assembly and enzymatic activity of the MSL complex, hence impacting on global H4K16ac levels. Transcriptome analysis from patient cells showed misregulation of cellular pathways involved in serotonergic signaling, morphogenesis, axon guidance and cell structure. Finally, using HDAC inhibitor treatment, we can rescue expression of downregulated target genes, offering potential therapeutic avenues for MSL3-mutated patients. Taken together, we characterize a novel syndrome, named ILyADe (Impaired Lysine 16 acetylation associated disorder), which is caused by mutations of an epigenetic regulator, allowing us for the first time to unravel the crucial role of H4K16ac during human development. ILyaDe thus constitutes a new class of syndromes associated with misregulation of a single epigenetic modification caused by a genetic alteration.

2018-09-18 | PXD009317 | Pride

Analysis of RNA-Seq with the deletion of components of the NSL complex

Project description:The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase complex consists of 9 subunits can acetylate histone H4K16, H4K5 and H4K8. NSL complex is essential for the multiple transcriptional regulation mechanisms. In this work, mRNA profiles of WT and NSL3 knockout 293T cells were generated by deep sequencing, in triplicate. qRT–PCR validation was performed using SYBR Green assays. we identified more than 100 genes as NSL complex transcriptional targets, including several transcription factors (TFs), such as Yin Yang 1 (YY1) which are mainly involved in cell proliferation, biological adhesion, and metabolic processes. the NSL complex regulates gene expression by forming a gene regulatory network with multiple TFs. It is conceivable that the NSL complex participates in the regulation of a variety of biological functions in cells.

2022-03-18 | GSE198646 | GEO

MOF-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation [ChIP-seq]

Project description:The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cells (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL (Male-Specific Lethal) and NSL (Non-specific lethal). The individual contribution of MSL and NSL complexes to transcription regulation in mESCs is not well understood. Our genome-wide analysis of MSL and NSL localization show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds at promoters, iii) while MSL binds in gene bodies. Knockdown of Msl1 leads to a global loss of histone H4K16ac indicating that MSL is the main HAT acetylating H4K16 in mESCs. MSL was enriched at many mESC-specific genes, but also at bivalent domains. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs. Furthermore, MSL is essential for the regulation of key mESC-specific and bivalent developmental genes. Genome-wide comparions of Msl1 and Nsl1 binding in mESCs

2014-06-04 | E-GEOD-53797 | biostudies-arrayexpress

MOF-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation [array]

Project description:The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cells (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL (Male-Specific Lethal) and NSL (Non-specific lethal). The individual contribution of MSL and NSL complexes to transcription regulation in mESCs is not well understood. Our genome-wide analysis of MSL and NSL localization show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds at promoters, iii) while MSL binds in gene bodies. Knockdown of Msl1 leads to a global loss of histone H4K16ac indicating that MSL is the main HAT acetylating H4K16 in mESCs. MSL was enriched at many mESC-specific genes, but also at bivalent domains. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs. Furthermore, MSL is essential for the regulation of key mESC-specific and bivalent developmental genes. Gene expression was analysed through microarrays in mESCs infected with shRNA vectors expressing either a non-target control, shRNA against Nsl1 or Msl1 to knockdown Nsl1 or Msl1.

2014-06-04 | E-GEOD-56646 | 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