Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mutant p53 regulates enhancer-associated H3K4 monomethylation through interactions with the methyltransferase MLL4

ABSTRACT: In this study, we establish a mechanism in which mutant p53 cooperates with MLL4 to regulate aberrant enhancer activity and tumor promoting gene expression in response to chronic TNF-a signaling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE115985 | GEO | 2018/06/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Mutant p53 regulates enhancer-associated H3K4 monomethylation through interactions with the methyltransferase MLL4.

Project description: Not available

| S-EPMC6109924 | biostudies-literature

Mutant p53 regulates enhancer-associated H3K4 monomethylation through interactions with the methyltransferase MLL4

Project description:Mutant p53 regulates enhancer-associated H3K4 monomethylation through interactions with the methyltransferase MLL4

| PRJNA476701 | ENA

The MLL3/MLL4 branch of the COMPASS family regulates H3K4 monomethylation at enhancers

Project description:Histone H3 lysine 4 (H3K4) can be mono-, di-, and trimethylated by members of the COMPASS (COMplex of Proteins ASsociated with Set1) family from yeast to human and these modifications can be found at distinct regions of the genome. Monomethylation of histone H3K4 (H3K4me1) is relatively more enriched at metazoan enhancer regions compared to trimethylated histone H3K4 (H3K4me3), which are found at transcription start sites in all eukaryotes. Our recent studies in Drosophila demonstrated that the Trithorax-related (Trr) branch of the COMPASS family regulates enhancer activity and is responsible for the implementation of H3K4me1 at these regions. There are six COMPASS family members in mammals, two of which, MLL3 and MLL4, are most closely related to Drosophila Trr. Here, we use ChIP-seq of this class of COMPASS family members in both human HCT116 cells and mouse embryonic stem cells and find that MLL4 is preferentially found at enhancer regions. MLL3 and MLL4 are frequently mutated in cancer, and indeed, the widely used HCT116 cancer cell line contains inactivating mutations in the MLL3 gene. Using HCT116 cells in which MLL4 has also been knocked out, we demonstrate that MLL4 is a major regulator of H3K4me1 in these cells, with the greatest loss of monomethylation at enhancer regions. Moreover, we found a redundant role between Mll3 and Mll4 in enhancer H3K4 monomethylation in mouse embryonic fibroblast (MEF) cells. These findings suggest that mammalian MLL3/MLL4 function in the regulation of enhancer activity and enhancer-promoter communication during gene expression and that mutations of MLL3 and MLL4 found in cancer could exert their properties through enhancer malfunction. ChIP-Seq in mouse embryonic stem (mES) cells for MLL4. ChIP-seq of MLL4 and p300 in human parental HCT116 cells. ChIP-seq of H3K4me1, H3K4me2 and H3K4me3 in parental HCT116 cells and HCT116 cells with Mll4∆set.

2013-09-30 | E-GEOD-51176 | biostudies-arrayexpress

Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

Project description: Not available

| S-EPMC3521626 | biostudies-literature

Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition.

Project description: Not available

| S-EPMC5081576 | biostudies-literature

Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation.

Project description: Not available

| S-EPMC5662137 | biostudies-literature

The MLL3/MLL4 branch of the COMPASS family regulates H3K4 monomethylation at enhancers

2013-09-30 | GSE51176 | GEO

H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation.

Project description: Not available

| S-EPMC3869375 | biostudies-literature

Mll3 and Mll4 facilitate enhancer RNA synthesis and transcriptional elongation from promoters independently of H3K4 monomethylation

Project description:Monomethylation of histone H3 at lysine 4 (H3K4me1) and acetylation of histone H3 at lysine 27 (H3K27ac) are correlated with transcriptionally engaged enhancer elements, but the functional impact of these modifications on enhancer activity is not well understood. Here we used CRISPR/Cas9 genome editing to separate catalytic activity-dependent and independent functions of Mll3 (Kmt2c) and Mll4 (Kmt2d, Mll2), the major enhancer H3K4 monomethyltransferases. Loss of Mll3/4 catalytic activity and H3K4me1 from enhancers causes partial depletion of H3K27ac, but surprisingly minor effects on enhancer Pol II binding, enhancer RNA (eRNA) transcription and gene expression. In contrast, loss of Mll3/4 proteins results in dramatic reduction of eRNA production, concomitant with impaired transcriptional elongation at adjacent promoters. Altogether our results suggest the major coactivator function of Mll3/4 is largely independent of H3K4me1 and instead linked to enhancer Pol II occupancy, eRNA transcription and long-range influence on elongation at target promoters.

2017-05-05 | GSE98063 | GEO

Interplay of BAF and MLL4 promotes enhancer activation

Project description:Cell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Using adipogenesis as a model system, we identify BAF as the major SWI/SNF complex that colocalizes with LDTFs and MLL4 on active enhancers during cell differentiation. Similar to MLL4, BAF is required for cell type-specific gene induction in adipogenesis. In contrast, another SWI/SNF complex PBAF is enriched on promoters and is dispensable for adipogenesis. By depleting BAF subunits SMARCA4 (BRG1) and SMARCB1 (SNF5) as well as MLL4 in cells, we show that BAF and MLL4 reciprocally regulate each other’s binding on active enhancers before and during adipogenesis. By focusing on enhancer activation by the adipogenic transcription factor C/EBPβ without inducing cell differentiation, we provide direct evidence to support an interdependent relationship between BAF and MLL4 in activating cell type-specific enhancers. Together, these findings suggest that the interplay of BAF and MLL4 promotes LDTF-dependent activation of cell type-specific enhancers.

2021-01-07 | GSE151115 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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