The cross-linking mass spectrometry (CX-MS) results of Human TIP60 complex (hTIP60)
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Suspension Culture
SUBMITTER: 
Ke Chen
LAB HEAD: Yanhui Xu
PROVIDER: PXD048625 | Pride | 2024-07-11
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Chenke-CK3-20230222_HCDFT.mgf | Mgf | |||
| Chenke-CK4-20230222_HCDFT.mgf | Mgf | |||
| Chenke_CK3_20230222.raw | Raw | |||
| Chenke_CK4_20230222.raw | Raw | |||
| checksum.txt | Txt |
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Project description:Background Tip60 (KAT5) is the histone acetyltransferase (HAT) of the mammalian Tip60/NuA4 complex. While Tip60 is important for early mouse development and mouse embryonic stem cell (mESC) pluripotency, the function of Tip60 as reflected in a genome-wide context is not yet well understood. Results Gel filtration of nuclear mESCs extracts indicate incorporation of Tip60 into large molecular complexes and exclude the existence of large quantities of âfreeâ Tip60 within the nuclei of ESCs. Thus, monitoring of Tip60 binding to the genome should reflect the behaviour of Tip60-containing complexes. The genome-wide mapping of Tip60 binding in mESCs by chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-seq) shows that the Tip60 complex is present at promoter regions of predominantly active genes that are bound by RNA polymerase II (Pol II) and contain the H3K4me3 histone mark. The coactivator HAT complexes, Tip60- and Mof (KAT8)-containing (NSL and MSL), show a global overlap at promoters, whereas distinct binding profiles at enhancers suggest different regulatory functions of each essential HAT complex. Interestingly, Tip60 enrichment peaks at about 200 bp downstream of the transcription start sites suggesting a function for the Tip60 complexes in addition to histone acetylation. The comparison of genome-wide binding profiles of Tip60 and c-Myc, a somatic cell reprogramming factor that binds predominantly to active genes in mESCs, demonstrate that Tip60 and c-Myc co-bind at 50â60 % of their binding sites. We also show that the Tip60 complex binds to a subset of bivalent developmental genes and defines a set of mESC-specific enhancer as well as super-enhancer regions. Conclusions Our study suggests that the Tip60 complex functions as a global transcriptional co-activator at most active Pol II promoters, co-regulates the ESC-specific c-Myc network, important for ESC self-renewal and cell metabolism and acts at a subset of active distal regulatory elements, or super enhancers, in mESCs. Genome- wide binding of Tip60 co-activator complexes
2015-11-06 | E-GEOD-69671 | biostudies-arrayexpress
Project description:Proper regulation of chromatin structure is necessary for the maintenance of cell type-specific gene expression patterns. The embryonic stem cell (ESC) expression pattern governs self-renewal and pluripotency. Here, we present an RNAi screen in mouse ESCs of 1008 loci encoding chromatin proteins. We identified 68 proteins that exhibit diverse phenotypes upon knockdown (KD), including seven subunits of the Tip60-p400 complex. Phenotypic analyses revealed that Tip60-p400 is necessary to maintain characteristic features of ESCs. We show that p400 localization to the promoters of both silent and active genes is dependent upon histone H3 lysine 4 trimethylation (H3K4me3). Furthermore, the Tip60-p400 KD gene expression profile is enriched for developmental regulators and significantly overlaps with that of the transcription factor Nanog. Depletion of Nanog reduces p400 binding to target promoters without affecting H3K4me3 levels. Together, these data indicate that Tip60-p400 integrates signals from Nanog and H3K4me3 to regulate gene expression in ESCs. Keywords: ChIP-chip We identified genes encoding subunits of the Tip60-p400 complex in an RNAi screen of chromatin proteins in mouse embryonic stem cells (ESCs), which upon depletion resulted in a dramatic phenotype. To investigate the role of this complex in gene expression in ESCs, we performed ChIP-chip location analysis using genome-wide promoter tiling arrays. We immunoprecipitated chromatin with an antibody to p400 and competitively hybridized it to input material on two arrays with probes interrogating essentially all mouse promoters with 100 bp tiling of -3250 bp to +750 bp around the transcription start sites.
2008-07-11 | E-GEOD-11241 | biostudies-arrayexpress
Project description:The human NuA4/TIP60 co-activator complex, a fusion of the yeast SWR1 and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4/H2A/H2A.Z to play crucial roles regulating gene expression and maintaining genome stability. Our cryo-EM studies show that within the NuA4/TIP60 complex, the EP400 subunit serves as an architectural scaffold holding the different functional modules in specific positions and giving rise to a novel arrangement of the ARP module. EP400 interacts with the TRRAP subunit using a footprint that overlaps with that of the SAGA acetyltransferase complex, thereby preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome,emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.
2024-08-08 | PXD053207 | Pride
Project description:The human NuA4/TIP60 co-activator complex, a fusion of the yeast SWR1 and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4/H2A/H2A.Z to play crucial roles regulating gene expression and maintaining genome stability. Our cryo-EM studies show that within the NuA4/TIP60 complex, the EP400 subunit serves as an architectural scaffold holding the different functional modules in specific positions and giving rise to a novel arrangement of the ARP module. EP400 interacts with the TRRAP subunit using a footprint that overlaps with that of the SAGA acetyltransferase complex, thereby preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.
2024-08-08 | PXD053209 | Pride
Project description:The human NuA4/TIP60 co-activator complex, a fusion of the yeast SWR1 and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4/H2A/H2A.Z to play crucial roles regulating gene expression and maintaining genome stability. Our cryo-EM studies show that within the NuA4/TIP60 complex, the EP400 subunit serves as an architectural scaffold holding the different functional modules in specific positions and giving rise to a novel arrangement of the ARP module. EP400 interacts with the TRRAP subunit using a footprint that overlaps with that of the SAGA acetyltransferase complex, thereby preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.
2024-08-06 | GSE261651 | GEO
Project description:The human NuA4/TIP60 co-activator complex, a fusion of the yeast SWR1 and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4/H2A/H2A.Z to play crucial roles regulating gene expression and maintaining genome stability. Our cryo-EM studies show that within the NuA4/TIP60 complex, the EP400 subunit serves as an architectural scaffold holding the different functional modules in specific positions and giving rise to a novel arrangement of the ARP module. EP400 interacts with the TRRAP subunit using a footprint that overlaps with that of the SAGA acetyltransferase complex, thereby preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.
2024-08-06 | GSE261650 | GEO
Project description:Environmental enrichment (EE) conditions have profound beneficial effects for reinstating cognitive ability in neuropathological disorders like Alzheimerâs disease (AD). While EE benefits involve epigenetic gene control mechanisms that comprise histone acetylation, the histone acetyltransferases (HATs) involved remain largely unknown. Here, we examine a role for Tip60 HAT action in mediating activity- dependent beneficial neuroadaptations to EE using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. We show that flies raised under EE conditions display enhanced MB axonal outgrowth, synapse protein production, histone acetylation induction and transcriptional activation of cognition linked genes when compared to their genotypically identical siblings raised under isolated conditions. Further, these beneficial changes are impaired in both Tip60 HAT mutant flies and APP neurodegenerative flies. While EE conditions provide only slight beneficial neuroadaptive changes in the APP neurodegenerative fly MB, such positive changes are significantly enhanced by increasing MB Tip60 HAT levels. Our results implicate Tip60 as a critical mediator of EE-induced benefits, and provide insight into synergistic behavioral and epigenetic based approaches for treatment of cognitive disorders. EE has been shown to positively impact gene expression profiles in the mouse brain that are enriched in functions such as neuronal structure, synaptic plasticity and neurotransmission. Thus, we asked whether the EE induced beneficial MB structural and synaptic changes we observe are accompanied by neuroadaptive transcriptional benefits in the Drosophila MB, and if so, is Tip60 HAT action required for this process. To address this question, we accessed EE induced beneficial transcriptional changes using microarray. We crossed our UAS-mCD8-GFP;Tip60E431Q flies or control UAS-mCD8-GFP flies to MB GAL4 OK-107 to simultaneously induce Tip60 HAT loss in the MB while tagging MB cells with GFP. Adult progeny were exposed to EE or ISO conditions. After conditioning, the GFP tagged MB Kenyon neurons were FACs purified from conditioned fly brains from each genotype to enrich for detection of an EE induced MB transcriptional response. RNA was isolated from the purified Kenyon MB neurons and transcriptional changes for each genotype were assessed using microarray analysis
2016-01-07 | E-GEOD-76612 | biostudies-arrayexpress
Project description:The Tip60 (also known as Kat5) lysine acetyltransferase functions broadly as a transcriptional co-activator that acetylates histones. In contrast, Tip60 functions in embryonic stem cells (ESCs) both to silence genes that promote differentiation and to activate genes required for proliferation. The mechanism by which Tip60 functions as a repressor is unknown. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs and is necessary for complete silencing of most differentiation genes targeted by Tip60. In contrast to differentiated cells, where Hdac6 is mainly cytoplasmic and does not interact with Tip60, Hdac6 is largely nuclear in ESCs and neural stem cells (NSCs) and interacts with Tip60-p400 in both cell types. Hdac6 is enriched at promoters bound by Tip60-p400 in ESCs, but while Tip60 binds on both sides of transcription start sites (TSSs), Hdac6 binding overlaps with only the downstream Tip60 peak. Surprisingly, Hdac6 does not deacetylate histones at these sites, but rather is required for Tip60 binding. These data suggest that nuclear exclusion of Hdac6 during differentiation plays a major role in modulation of Tip60-p400 function. We determined the genome-wide localization of Tip60 and Hdac6 in mouse ES cells, and examined genomic binding profiles of Tip60 and Hdac6 upon indicated knockdown by ChIP-seq. We examined genomic binding profiles of p400 upon indicated knockdown by ChIP-seq.
2013-11-20 | E-GEOD-42209 | biostudies-arrayexpress
Project description:Rhodococcus sp. CX strain:CX Genome sequencing and assembly
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