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E-GEOD-50459 - mRNA expression profiles of WT and MLL4-/- after MyoD-induced myogenesis

Status
Released on 17 December 2013, last updated on 3 June 2014
Organism
Mus musculus
Samples (4)
Protocols (3)
Description
Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for the deposition of H3K4me1/2 on enhancers remain elusive. Furthermore, the functions of these methyltransferases on enhancers and associated cell-type-specific gene expression are poorly understood. Here, we identify MLL4 (KMT2D) as a major H3K4 mono- and di-methyltransferase in mammalian cells. Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of MLL4 dramatically decreases H3K4me1/2 and H3K27ac on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Finally, we provide evidence that lineage-determining TFs recruit and require MLL4 to establish enhancers critical for cell-type-specific gene expression. Together, these results identify MLL4 as an H3K4 mono-/di-methyltransferase required for enhancer activation during cell differentiation. RNA-Seq analysis of mRNA profiles in adenoviral GFP- or Cre-infected MLL3-/-;MLL4-flox/flox cells. Preadipocytes: brown preadipocytes before differentiation. D5 myocytes: 5 days after MyoD-induced myogenesis of brown preadipocytes.
Experiment type
RNA-seq of coding RNA 
Contacts
Chaochen Wang, Ji-Eun Lee, Kai Ge, Shiliyang Xu, Weiqun Peng
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-50459.idf.txt
Sample and data relationshipE-GEOD-50459.sdrf.txt
Processed data (1)E-GEOD-50459.processed.1.zip
Links