ChIP-seq of MLL3 Delta mice liver and wild-type littermate controls
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Mus musculus
SUBMITTER: Matthew Baxter
PROVIDER: E-MTAB-11203 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:ChIP-seq of MLL3 Delta mice liver and wild-type littermate controls
| PRJEB49028 | ENA
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
Project description:FOXA1 is a pioneer factor that is important in hormone dependent cancer cells to stabilise nuclear receptors, such as estrogen receptor (ER) to chromatin. FOXA1 binds to enhancers regions that are enriched in H3K4mono- and dimethylation (H3K4me1, H3K4me2) histone marks and evidence suggests that these marks are requisite events for FOXA1 to associate with enhancers to initate subsequent gene expression events. However, exogenous expression of FOXA1 has been shown to induce H3K4me1 and H3K4me2 signal at enhancer elements and the order of events and the functional importance of these events is not clear. We performed a FOXA1 Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells in order to identify FOXA1 interacting partners and we found histone-lysine N-methyltransferase (MLL3) as the top FOXA1 interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition, in line with our observation that MLL3 associates with an enhancer specific protein. We performed MLL3 ChIP-seq in breast cancer cells and unexpectedly found that MLL3 binds mostly at non-promoter regions enhancers, in contrast to the prevailing hypothesis. MLL3 was shown to occupy regions marked by FOXA1 occupancy and as expected, H3K4me1 and H3K4me2. MLL3 binding was dependent on FOXA1, indicating that FOXA1 recruits MLL3 to chromatin. Motif analysis and subsequent genomic mapping revealed a role for Grainy head like protein-2 (GRHL2) which was shown to co-occupy regions of the chromatin with MLL3. Regions occupied by all three factors, namely FOXA1, MLL3 and GRHL2, were most enriched in H3K4me1. MLL3 silencing decreased H3K4me1 at enhancer elements, but had no appreciable impact on H3K4me3 at enhancer elements. We identify a complex relationship between FOXA1, MLL3 and H3K4me1 at enhancers in breast cancer and propose a mechanism whereby the pioneer factor FOXA1 can interact with a chromatin modifier MLL3, recruiting it to chromatin to facilitate the deposition of H3K4me1 histone marks, subsequently demarcating active enhancer elements.
2016-12-12 | PXD005253 | Pride
Project description:MLL3 inactivation mutations occurs frequently in human breast cancer. To understand the function of MLL3 inactivation, we compared the gene expression profiles of the vector control (WT) and Mll3-knockout MCF7 cells generated by CRISPR-CAS9. Affymetrix human Gene 2.0ST arrays were used for microarray.
2022-10-08 | GSE171445 | GEO
Project description:MLL3 inactivation mutations occurs frequently in human breast cancer. To understand the function of MLL3 inactivation, we compared the gene expression profiles of the vector control (WT) and Mll3-null mouse mammary stem cells generated by CRISPR. Affymetrix mouse Gene 2.0ST ships were used for microarray.
2016-09-19 | GSE79946 | GEO
Project description:To determine the effect of Mll3 deletion on H3K4me3 Chip signals in intestinal stem cell populations. This data has been described in the following article : Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin. Boles MK et al PLoS Genet. 2009 Dec;5(12) and its further analysis can be freely submitted for publication. For information on the proper use of data shared by the Wellcome Trust Sanger Institute (including information on acknowledgement), please see http://www.sanger.ac.uk/datasharing/ Abstract: Briefly we wanted to determine the effect of Mll3 deletion on H3K4me3 binding in cells of the intestine and to compare these to the H3K4me3 pattern found in wildtype animals.
2011-12-15 | E-ERAD-42 | biostudies-arrayexpress
Project description:a.Background Cancer resequencing studies have revealed epigenetic enzymes as common targets for recurrent mutations. The monomethyltransferase MLL3 is among the most recurrently mutated enzymes in ER+ breast cancer. The H3K4me1 marks created by MLL3 can define enhancers. In ER+ breast cancer, ERα genome binding sites are primarily distal enhancers. Thus, we hypothesize that mutation of MLL3 will alter the genomic binding and transcriptional regulatory activity of ERα. b.Methods We investigated the genomic consequences of knocking down MLL3 in an MLL3/PIK3CA WT ER+ breast cancer cell line. c. Results Loss of MLL3 led to large loss of H3K4me1 across the genome, and a shift in ERα binding sites, which was accompanied by a re-organization of the breast cancer transcriptome. Enrichment analyses of ERα binding sites in MLL3 KD identified endocrine therapy resistance terms, and we show that MLL3 KD cells are resistant to tamoxifen and fulvestrant. Many differentially expressed genes are controlled by new locations of H3K4me1 deposition and ERα binding, suggesting that loss of functional MLL3 leads to new transcriptional regulation of essential genes. Motif analysis of RNA-seq and ChIP-seq data highlighted SP1 as a critical transcription factor in the MLL3 KD cells. Loss of ERα binding is accompanied by a massive increase in SP1 binding at differentially expressed genes. d.Conclusions Our data show that loss of functional MLL3 leads to endocrine therapy resistance. This highlights the importance of genotyping patient tumor samples for MLL3 mutation upon initial resection, prior to deciding upon treatment plans.
2020-12-16 | GSE163264 | GEO
Project description:Analysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623 Young adult female mGFAP-Cre-RiboTag or mGFAP-Cre-RiboTag-STAT3-LoxP mice underwent severe crush SCI at thoracic level 10. 14 days following SCI, the central 3mm of the SCI lesion was extracted, homogenized and (i) astrocyte-specific ribosome-associated RNA (ramRNA) precipitated via a hemagglutinin (HA) tag targeted to either WT (n=4) or STAT3-CKO (n=3) astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples. Sex and age-matched mGFAP-Cre-RiboTag mice served as uninjured controls (n=4).
2016-03-30 | E-GEOD-76097 | biostudies-arrayexpress
Project description:We performed MLL3 ChIP-seq in breast cancer cells and unexpectedly found that MLL3 binds mostly at non-promoter regions enhancers, in contrast to the prevailing hypothesis. MLL3 was shown to occupy regions marked by FOXA1 occupancy and as expected, H3K4me1 and H3K4me2. MLL3 binding was dependent on FOXA1, indicating that FOXA1 recruits MLL3 to chromatin. Motif analysis and subsequent genomic mapping revealed a role for Grainy head like protein-2 (GRHL2) which was shown to co-occupy regions of the chromatin with MLL3. Regions occupied by all three factors, namely FOXA1, MLL3 and GRHL2, were most enriched in H3K4me1. MLL3 silencing decreased H3K4me1 at enhancer elements, but had no appreciable impact on H3K4me3 at enhancer elements. We identify a complex relationship between FOXA1, MLL3 and H3K4me1 at enhancers in breast cancer and propose a mechanism whereby the pioneer factor FOXA1 can interact with a chromatin modifier MLL3, recruiting it to chromatin to facilitate the deposition of H3K4me1 histone marks, subsequently demarcating active enhancer elements.
2016-12-06 | GSE81714 | GEO
Project description:MLL3 is a histone H3K4 methyltransferase which is frequently mutated in cancer, but the underlying molecular mechanisms remain elusive. Here, we found that MLL3 knockout by CRISPR/sgRNA did not elevate proliferation rate of cancer cells, but significantly enhanced cell migration. Through RNA-Seq and ChIP-Seq approaches, we identified TNS3 as the potential target gene for MLL3. MLL3 depletion caused down regulation of H3K4me1 and H3K27ac on an enhancer ~ 8 kb ahead of TNS3. 3C assay indicated the identified enhancer interacts with TNS3 promoter, and repression of enhancer with dCas9-KRAB system impaired TNS3 expression. Exogenous expression of TNS3 in MLL3 deficient cells completely blocked the enhanced cell migration phenotype. Taken together, our study revealed a novel mechanism for MLL3 in suppressing cancer, which may provide novel targets for diagnosis or drug development.
2021-04-14 | GSE160253 | GEO