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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198646 | GEO | 2022/03/18

REPOSITORIES: GEO

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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

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

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 | PXD022267 | Pride

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

2021-06-29 | PXD021943 | 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

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

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 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.

2021-02-28 | GSE157583 | GEO

Analysis of NSL knockout brains

Project description:In the current study, we analyse the function of MOF-NSL complex in neural cells. We find that the NSL complex regulates metabolic networks in the brain.

2020-03-31 | GSE138981 | GEO

ChIP-Seq of NSL3 and MBD-R2 in Drosophila melanogaster S2 cells to investigate the function of Non-Specific Lethal (NSL) complex

Project description:The major H4K16 acetylase MOF has been found in two complexes, the Male-Specific Lethal (MSL) and the Non-Specific Lethal (NSL) complex. The latter one consists of at least 7 members: NSL1, NSL2, NSL3, MBD-R2, MCRS2, WDS, and MOF. To investigate it's function, we performed genome-wide profiling of NSL3 and MBD-R2 in S2 cells. In addition, we obtained ChIP-Seq profiles for NSL1 and MCRS2 from 3rd instar larvae salivary glands that can be accessed via the accession number E-MTAB-214. This submission is also related to E-MTAB-1084.

2012-06-19 | E-MTAB-1085 | biostudies-arrayexpress

The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset

Project description:This SuperSeries is composed of the following subset Series: GSE30989: MOF-containing NSL complex specifically binds promoters of most, but stimulates only a specific subset of, housekeeping genes (ChIP-chip dataset) GSE30990: MOF-containing NSL complex specifically binds promoters of most, but stimulates only a specific subset of, housekeeping genes (expression dataset) Refer to individual Series

2011-10-28 | E-GEOD-30991 | biostudies-arrayexpress

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