MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [CUT&RUN]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1073244 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27868248_1.fastq.gz | Fastqsanger.gz | |||
| SRR27868248_2.fastq.gz | Fastqsanger.gz | |||
| SRR27868249_1.fastq.gz | Fastqsanger.gz | |||
| SRR27868249_2.fastq.gz | Fastqsanger.gz | |||
| SRR27868250_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 72 |
Similar Datasets
Project description:MLL3 and MLL4 are the mjor histone lysine methyltransferases for the active enhance mark H3K4me1. We observed that platelet counts are dramatically decreased in the MLL3/4 SET-deletion mice. Cultured megakaryocytes from MLL3/4 SET-deletion fetal liver were used for RNA-seq analysis to investigate the changes in gene expression. We also performed CUT&RUN analysis to examine the changes in enhncers that may regulate those gene expression. We included PTIP in this study, because it is an important co-factor of the MLL3/4 complex, and knockout of PTIP also leads to decreased platelet production.
2025-05-13 | GSE255021 | GEO
Project description:MLL3 and MLL4 are the mjor histone lysine methyltransferases for the active enhance mark H3K4me1. We observed that platelet counts are dramatically decreased in the MLL3/4 SET-deletion mice. Cultured megakaryocytes from MLL3/4 SET-deletion fetal liver were used for RNA-seq analysis to investigate the changes in gene expression. We also performed CUT&RUN analysis to examine the changes in enhncers that may regulate those gene expression. We included PTIP in this study, because it is an important co-factor of the MLL3/4 complex, and knockout of PTIP also leads to decreased platelet production.
2025-05-13 | GSE255020 | GEO
Project description:MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [RNA-seq]
| PRJNA1073243 | ENA
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:Enhancers are essential in defining cell fates through the control of cell type specific gene expression. Enhancer activation is a multi-step process involving chromatin remodelers and histone modifiers. One of these steps is monomethylation of H3K4 (H3K4me1) by MLL3 (KMT2C) and MLL4 (KMT2D). MLL3/4 are thought to be critical for enhancer activation and cognate gene expression including through the recruitment of acetyltransferases for H3K27. Here we test this model by evaluating the impact of MLL3/4 loss on chromatin and transcription during early embryonic stem cell differentiation. We find that MLL3/4 activity is required at most if not all sites that gain or lose H3K4me1, but is largely dispensable at sites that remain stably methylated during this transition. This requirement extends to H3K27 acetylation (H3K27ac) at most transitional sites. Unexpectedly, many sites gain H3K27ac independent of MLL3/4 or H3K4me1 including enhancers regulating key factors in early differentiation. Furthermore, despite the failure to gain active histone marks at thousands of enhancers, transcriptional activation of nearby genes is largely unaffected, thus uncoupling the regulation of chromatin state from transcriptional changes during this transition. These data challenge current models of enhancer activation and imply distinct mechanisms between stable and dynamically changing enhancers. Moreover, the data suggest limited roles for many enhancers in transcriptional regulation in early ESC differentiation. Collectively, our study highlights gaps in knowledge about the steps and epistatic relationships of enzymes necessary for enhancer activation and cognate gene transcription.
2023-01-23 | GSE212949 | 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-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: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