Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA391896 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5755570.fastq.gz | Fastqsanger.gz | |||
| SRR5755580_1.fastq.gz | Fastqsanger.gz | |||
| SRR5755580_2.fastq.gz | Fastqsanger.gz | |||
| SRR5755571.fastq.gz | Fastqsanger.gz | |||
| SRR5755581_1.fastq.gz | Fastqsanger.gz |
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Project description:The histone variant H2A.Z is essential for maintaining the identity of embryonic stem cell (ESC) by keeping bivalent developmental genes at a poised state. However, how H2A.Z is deposited into the bivalent domains remains unknown. In mammals, two chromatin-remodeling complexes, Tip60/p400 and SRCAP, exchange the canonical histone H2A for H2A.Z in the chromatin. Here we show that Glioma Amplified Sequence 41 (Gas41), a shared subunit of the two H2A.Z-depositing complexes, functions as a reader of histone acetylation and recruits Tip60/p400 and SRCAP to deposit H2A.Z into specific chromatin regions including bivalent domains. The YEATS domain of Gas41 bound to acetylation on histone H3K27 and H3K14 both in vitro and in cells. Crystal structure of the Gas41 YEATS domain in complex with the H3K27ac peptide revealed that, similar to the AF9 and ENL YEATS domains, Gas41 YEATS forms a serine-lined aromatic cage for Kac recognition; mutations of either the aromatic residues of YEATS domain or the nearby residue of H3K27 abrogated the interaction. In mESCs, knockdown of Gas41 led to cell differentiation as the result of derepression of differentiation genes. Importantly, the differentiated morphology was rescued by expressing wild type Gas41, but not the YEATS domain mutated counterparts that do not recognize histone acetylation. Mechanically, we found that Gas41 depletion led to reduction of H2A.Z levels and a concomitant reduction of H3K27me3 levels at the promoters of a subset of bivalent genes. Together, our study identifies the Gas41 YEATS domain as a reader of histone acetylation and establishes a link between histone acetylation and H2A.Z deposition in the maintenance of ESC identity.
2018-07-01 | GSE100460 | GEO
Project description:Both, acetylation of histones and of histone variant H2A.Z are conserved features of eukaryotic transcription start sites (TSSs) and both features appear to be critical for correct transcription initiation. However, complex patterns of transcriptional regulation have complicated the establishment of functional links between histone acetylation, H2A.Z deposition and their importance in transcription regulation. To elucidate these links, we took advantage of the unusual genome organization in Trypanosoma brucei, a highly divergent eukaryote. In T. brucei genes are organized in long polycistronic transcription units, drastically reducing the sites of transcription initiation. Employing a highly sensitive and quantitative mass-spectrometry-based approach, we quantified the genome-wide histone acetylation and methylation pattern and identified various acetyl and methyl marks exclusively enriched at TSSs In addition, we show that deletion of histone acetyltransferase 2 results in a loss of H4 acetylation at TSSs, a loss of H2A.Z deposition at TSSs and a shift in the sites of transcription initiation. Combined, our findings demonstrate an evolutionary conserved link between histone H4 acetylation, H2A.Z deposition and RNA transcription initiation.
2020-03-24 | PXD014452 | Pride
Project description:Histone acetylation is associated with active transcription in eukaryotic cells. It helps to open up the chromatin by neutralizing the positive charge of histone lysine residues, and by providing binding platforms for “reader” proteins. The bromodomain (BRD) has long been thought to be the sole protein module that recognizes acetylated histones. Recently, we identified the YEATS domain of AF9 as a novel acetyllysine-binding module, and showed that the ENL YEATS domain is an essential acetyl-histone reader in acute myeloid leukemias. The human genome encodes four YEATS domain proteins, including GAS41; however, the importance of the GAS41 YEATS domain, in human cancer remains largely unknown. Here we report that GAS41 is frequently amplified in human non-small cell lung cancer (NSCLC) and is required for cancer cell proliferation, survival, and transformation. Biochemical and crystal structural studies demonstrate that GAS41 binds to histone H3 acetylated on H3K27 and H3K14, a specificity that is distinct from that of AF9 or ENL. ChIP-seq analyses in lung cancer cells reveal that GAS41 colocalizes with H3K27ac and H3K14ac on the promoters of actively transcribed genes. Depletion of GAS41 or disruption of the interaction between its YEATS domain and acetylated histones impairs the association of histone variant H2A.Z with chromatin, and consequently, suppresses cancer cell growth and survival both in vitro and in vivo. Overall, our study identifies GAS41 as a histone acetylation reader that controls a transcriptional program essential for NSCLC tumorigenesis by modulating histone H2A.Z deposition.
2018-07-01 | GSE100347 | GEO
Project description:The goal was to investigate genome-wide if JAZF1 influences the deposition as well as the acetylation of the histone variant H2A.Z. ChIP-seq analysis revealed that depletion of JAZF1 leads to reduced acetylation of H2A.Z at specific sites.
2021-02-22 | GSE163318 | GEO
Project description:Histone lysine acetylation and methylation regulate gene transcription through coordination of chromatin structure and transcriptional activity. However, our understanding of the role of histones in gene regulation is far from complete, in part due to newly discovered novel histone modifications, whose functions are yet to be uncovered1. Here we report that histone H3 lysine 27 crotonylation (H3K27cr) is selectively recognized by the YEATS domain of GAS41 in association with SIN3a-HDAC1/2 co-repressor complex for gene transcriptional repression. The GAS41 YEATS domain dimer binds proto-oncogenic transcription factor c-Myc, which recruits GAS41/SIN3a-HDAC1/2 complex to target gene loci in chromatin such as cell cycle inhibitor p21. Transcriptional de-repression of p21, directed by tumor suppressor p53 upon doxorubicin stimulation, entails dissociation of c-Myc/GAS41/SIN3a-HDAC1/2 complex from chromatin, reduced H3K27 crotonylation, and consequentially increased H3K27 acetylation at p21 locus. GAS41 knockout or H3K27cr binding depletion with CRISPR/Cas9 results in p21 activation, cell cycle arrest and tumor growth inhibition in mice. Our study explains mechanistically causal effect of GAS41 and c-Myc gene amplification on down-regulation of p21 in human colorectal cancer, and suggests GAS41 as an anti-cancer target. We propose that H3K27 crotonylation represents a previously unrecognized, distinct chromatin state for gene transcriptional repression in contrast to H3K27 trimethylation for long-term transcriptional silencing and H3K27 acetylation for transcriptional activation.
2023-10-03 | GSE128590 | GEO
Project description:The histone variant H2A.Z plays key roles in gene expression, DNA repair, and centromere function. H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes that catalyze the nucleosomal exchange of canonical H2A with H2A.Z. Here we report that acetylation of histone H3 lysine 56 (H3-K56Ac) alters the substrate specificity of SWR-C, leading to promiscuous dimer exchange where either H2A.Z or H2A can be exchanged from nucleosomes. This result is confirmed in vivo, where genome-wide analysis demonstrates widespread decreases in H2A.Z levels in yeast mutants with hyperacetylated H3K56. Our work also suggests that a conserved SWR-C subunit may function as a M-bM-^@M-^\lockM-bM-^@M-^] that prevents removal of H2A.Z from nucleosomes. Our study identifies a histone modification that regulates a chromatin remodeling reaction and provides insights into how histone variants and nucleosome turnover can be controlled by chromatin regulators. H2A.Z ChIP seq experiments in mutants with constitutive H3K56ac
2013-04-15 | E-GEOD-43935 | biostudies-arrayexpress
Project description:Recognition of histone acetylation by the GAS41 YEATS domain promotes H2A.Z deposition and tumorigenesis of non-small cell lung cancer
| PRJNA391417 | ENA
Project description:Here, through genome-wide CRISPR-Cas9 screenings, we identified GAS41, a well-known histone reader as a major repressor for ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter independent of NRF2 binding. Notably, by bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes significantly to its oncogenic role in vivo. These data demonstrate that GAS41 is an important target for modulating tumor growth through ferroptosis. Our study reveals a previously unanticipated mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin and provides a model that the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).
2024-03-01 | GSE256462 | GEO
Project description:The variant histone H2A.Z is inserted into nucleosomes immediately downstream of promoters and is important for transcription. The site-specific deposition of H2A.Z is catalyzed by SWR, a conserved chromatin remodeler with affinity for promoter-proximal nucleosome depleted regions (NDRs) and histone acetylation. By comparing the genomic distribution of H2A.Z in wild-type and SWR-deficient cells, we found that SWR is also responsible for depositing H2A.Z at thousands of non-canonical sites not directly linked to NDRs or histone acetylation. To understand the targeting mechanism of H2A.Z, we presented SWR with a library of nucleosomes isolated from yeast and characterized those preferred by SWR. We found that SWR prefers nucleosomes associated with intergenic over coding regions, especially when polyadenine tracks are present. Insertion of polyadenine sequences into recombinant nucleosomes near the H2A-H2B binding site stimulated the H2A.Z insertion activity of SWR. Therefore, the genome is encoded with information contributing to remodeler-mediated targeting of H2A.Z.
2024-01-13 | GSE252824 | GEO
Project description:Post-translational histone modifications and the dynamics of histone variant H2A.Z are key mechanisms underlying the floral transition. In yeast, SWR1-C and NuA4-C mediate the deposition of H2A.Z and the acetylation of histone H4, H2A and H2A.Z respectively. Yaf9 is a subunit shared by both chromatin remodeling complexes. The significance of the two Arabidopsis YAF9 homologs, YAF9A and YAF9B, is unknown. We performed a transcriptomic analysis of wild-type and yaf9a yaf9b double mutant seedlings in order to reveal target genes whose transcription is regulated by YAF9 proteins.
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