Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global analysis of H3K4 methylation

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE18261: Expression analysis on Mll1+/+ and Mll1-/- MEFs GSE18262: ChIP-chip with antibodies for histone 3 lysine 4 trimethylation and histone 3 in Mll1+/+ and Mll1-/- MEFs GSE18263: ChIP-chip with antibodies for histone 3 lysine 4 trimethylation in Mll3+/+ and Mll3-/- MEFs and Ptip+/+ and Ptip-/- MEFs GSE18264: ChIP-chip with antibodies for histone 3 lysine 4 trimethylation, histone 3, and PolII in Mll1+/+ and Mll1-/- MEFs Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Pengfei Wang

PROVIDER: E-GEOD-18258 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II.

Wang Pengfei P Lin Chengqi C Smith Edwin R ER Guo Hong H Sanderson Brian W BW Wu Min M Gogol Madelaine M Alexander Tara T Seidel Christopher C Wiedemann Leanne M LM Ge Kai K Krumlauf Robb R Shilatifard Ali A

Molecular and cellular biology 20090824 22

A common landmark of activated genes is the presence of trimethylation on lysine 4 of histone H3 (H3K4) at promoter regions. Set1/COMPASS was the founding member and is the only H3K4 methylase in Saccharomyces cerevisiae; however, in mammals, at least six H3K4 methylases, Set1A and Set1B and MLL1 to MLL4, are found in COMPASS-like complexes capable of methylating H3K4. To gain further insight into the different roles and functional targets for the H3K4 methylases, we have undertaken a genome-wid ...[more]

PMID: 19703992

Similar Datasets

Project description:Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II A common landmark of activated genes is the presence of trimethylation on lysine 4 of histone H3 (H3K4) at promoter regions. The Set1/COMPASS was the founding member and the only H3K4 methylases in S. cerevisiae, however, in mammals at least six H3K4 methylases Set1A/B and MLL1-4 are found in COMPASS-like complexes capable of methylating H3K4. To gain further insight into the different roles and functional targets for the H3K4 methylases, we have undertaken a genome-wide analysis of H3K4 methylation pattern in wild-type Mll1+/+ and Mll1-/- mouse fibroblasts (MEFs). We found that Mll1 is required for the H3K4 trimethylation of less than 5% of promoters carrying this modification. Many of these genes, which include developmental regulators such as Hox genes show decreased levels of RNA polymerase II recruitment and expression concomitant with the loss of H3K4 methylation. Although Mll1 is only required for the methylation of a subset of Hox genes, Menin, a component of the Mll1 and Mll2 complexes, is required for the overwhelming majority of H3K4 methylation at Hox loci. However, the loss of MLL3/4 and/or the Set1 complexes have little to no effect on the Hox loci H3K4 methylation or expression levels in these MEFs. Together these data provide insight into redundancy and specialization of COMPASS-like complexes in mammals and provide evidence on a possible role for Mll1-mediated H3K4 methylation in the regulation of transcriptional initiation. Chromatin Immunoprecipitation was performed with antibodies for histone 3 lysine 4 trimethylation, histone 3, and PolII in Mll1+/+ and Mll1-/- mouse embryonic fibroblasts. DNA was hybridized to a custom Agilent tiling array (4x44k format) that covers three of the hox regions (A,B,D) and a collection of other genes.

Project description:Methylation of histone H3 lysine 4 (H3K4me) at actively expressed, cell type-specific genes is established during development by the Trithorax group of epigenetic regulators. In mammals, the Trithorax family includes KMT2A-D (MLL1-4), a family of SET domain proteins that function in large complexes to impart mono-, di-, and trimethylation at H3K4. Individual KMT2s and their co-factors are essential for embryonic development and the establishment of correct gene expression patterns, presumably by demarcating the active and accessible regions of the genome in a cell specific and heritable manner. Despite the importance of H3K4me marks in development, little is known about the importance of histone methylation in maintaining gene expression patterns in fully differentiated and non-dividing cell types. In this report, we utilized an inducible cardiac-specific Cre driver to delete the PTIP protein, a key component of a H3K4me complex, and ask whether this activity is still required to maintain the phenotype of terminally differentiated cardiomyocytes. Our results demonstrate that reducing the H3K4me3 marks is sufficient to alter gene expression patterns and significantly augment systolic heart function. These results clearly show that maintenance of H3K4me3 marks is necessary for the stability of the transcriptional program in differentiated cells. The array we performed allowed us to identify genes that are regulated by PTIP and histone methylation. 8-week-old littermate mice on a mixed C57B6 and B6129 background were utilized. Three mice were on a background with a PTIP floxed allele and a wild type PTIP allele (PTIP+1, PTIP+2, PTIP+3). Three mice had a transgene that expresses a modified estrogen receptor -Cre recombinase fusion protein under the control of a cardiac-specific driver (alpha myosin heavy chain, Jackson Lab stock #005650) and a floxed PTIP allele and a null PTIP (PTIPKO1, PTIPKO2, PTIPKO3). Both groups of mice were injected with tamoxifen at 8 weeks of age. Tamoxifen deletes the floxed PTIP allele in the PTIPKO mice. 5 days after tamoxifen injection, RNA was harvested from left ventricle (LV) apices in both groups. RNA was then sent to the University of Michigan microarray facility core for analysis.

Dataset Information

Global analysis of H3K4 methylation

Publications

Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure