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Series GSE52071 Query DataSets for GSE52071
Status Public on Jan 20, 2014
Title Mll2 is required for H3K4 trimethylation on bivalent promoters in ES cells whereas Mll1 is redundant
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Trimethylation of histone 3 lysine 4 (H3K4me3) at promoters of actively transcribed genes is a universal epigenetic mark and a key product of Trithorax-Group action. Here we show that Mll2, one of the six Set1/Trithorax-type H3K4 methyltransferases in mammals, is required for trimethylation of bivalent promoters in mouse embryonic stem cells. Mll2 is bound to bivalent promoters but also to most active promoters, which do not require Mll2 for H3K4me3 or mRNA expression. In contrast, the Set1 complex (Set1C) subunit Cxxc1 is primarily bound to active but not bivalent promoters. This indicates that bivalent promoters rely on Mll2 for H3K4me3 whereas active promoters have more than one bound H3K4 methyltransferase including Set1C. Removal of Mll1, sister to Mll2, had almost no effect on any promoter unless Mll2 was also removed indicating functional back-up between these enzymes. Except for a subset, loss of H3K4me3 on bivalent promoters did not prevent responsiveness to retinoic acid thereby arguing against a priming model for bivalency. In contrast, we propose that Mll2 is the pioneer trimethyltransferase for promoter definition in the naïve epigenome and Polycomb-Group action on bivalent promoters blocks premature establishment of active, Set1C bound, promoters.
Overall design ChIP-Seq to study MLL2 function using H3K4me3 (12 samples), H3K27me3 (4 samples), Pol2 (1 sample) or GFP (7 samples) antibody, and 6 RNA-Seq profiles
Contributor(s) Marks H, Denissov S, Hofemeister H, Kranz A, Ciotta G, Singh S, Anastassiadis K, Stunnenberg HG, Stewart AF
Citation(s) 24423662
Submission date Nov 04, 2013
Last update date May 15, 2019
Contact name Hendrik Marks
Organization name Radboud University Nijmegen, RIMLS
Department Molecular Biology
Street address Geert Grooteplein 26/28
City Nijmegen
ZIP/Postal code 6525GA
Country Netherlands
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (30)
GSM1258237 E14_H3K4me3
GSM1258238 MLL2KO_H3K4me3
GSM1258239 E14_Cxxc1_GFP
BioProject PRJNA226617
SRA SRP032533

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Supplementary file Size Download File type/resource
GSE52071_RAW.tar 1.4 Gb (http)(custom) TAR (of BED, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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