H1299 cells, DLG-41- or DLG-41nc- treated differential gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE295002 | GEO | 2026/02/11
REPOSITORIES: GEO
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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:H1299 cells, DLG-41- or DLG-41nc- treated differential gene expression
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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.
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Project description:H1299 cells were treated with 1.5uM AVJ16 or DMSO for 96 hours and then analyzed by MS
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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.
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Project description:Purpose: finding differential transcripts usage in environmentally harzardous chemical, methylparaben Methods: transcriptome analysis by the RNA-seq via mRNA pull-down Results: We found that methylparaben increases cellular toxicity in H1299 cells. Also, over thousands of retained intron events were detected from the RNA-seq analysis. Conclusions: Methylparaben increases cytotoxic effects in H1299 cells through the caspase-3 pathway and changes the context of trascript through the splicing regulation mechanisms.
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Project description:H3K27ac Hi-ChIP analysis was performed in MOLT-4 and DND-41 cells to analyze active chromatin-chromatin interactions after DMSO or ACBI-1 treatment.
2024-07-02 | GSE230591 | GEO
Project description:Cut&Run analysis was performed in DND-41 cells to analyze the basal level of H3K27ac and DNA bindings of BRG1 and RUNX1 after DMSO or ACBI-1 treatment.
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Project description:Nuclear morphology is normally maintained in a defined manner within a given cell type, and aberrant nuclear morphology correlates with a wide range of human diseases. However, the underlying mechanisms that define nuclear morphology are largely unknown. Here we show that depletion of YEATS family protein-GAS41 exhibits striking nuclear shape abnormalities.The misshapen nuclei can be rescued by GAS41 wild type, but not by GAS41 Y74A W93A mutant deficient in histone H3 lysine 27 acetylation (H3K27ac) binding. GAS41 depletion significantly decreased the expression of multiple genes encoding nuclear envelope (NE) architecture components including LMNB1, LMNB2, SYNE4 and LEMD2, and dysregulation of these genes directly leads to nuclear shape abnormalities. Using mass spectrometry and ChIP sequencing, we found GAS41 interacts with BRD2 and mediator components MED14 /MED23, and co-localizes with H3K27ac and BRD2 at target gene loci. The occupancy of BRD2 and MED14/MED23 at LMNB1, LMNB2, SYNE4 and LEMD2 is dependent on the presence of GAS41. Depletion of GAS41 or disruption of GAS41-H3K27ac recognition abrogated GAS41 binding at these gene loci, which further prevents the enrichment of BRD2, mediator complex as well as RNA polymerase II, thus consequently deactivated target gene expression and leading to nuclear morphology abnormalities. Overall, our study identified GAS41 as a novel nuclear shape regulator that works in concert with BRD2/mediator complex to control nuclear morphology
2025-10-01 | GSE182548 | GEO