Journal
MOLECULAR CELL
Volume 65, Issue 3, Pages 460-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2017.01.013
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Funding
- Robert H. Lurie Comprehensive Cancer Center - Translational Bridge Program Fellowship in Lymphoma Research
- Ia Convocatoria de Ayudas Fundacion BBVA a Investigadores, Innovadores y Creadores Culturales
- NIH [T32CA080621, R01CA101774, R50CA211428, R35CA197569]
- Spanish Ministerio de Educacion y Ciencia [SAF2013-48926-P]
- AGAUR
- ICREA Funding Source: Custom
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The spatiotemporal regulation of gene expression is central for cell-lineage specification during embryonic development and is achieved through the combinatorial action of transcription factors/co-factors and epigenetic states at cis-regulatory elements. Here, we show that in addition to implementing H3K4me3 at promoters of bivalent genes, Mll2 (KMT2B)/COMPASS can also implement H3K4me3 at a subset of non-TSS regulatory elements, a subset of which shares epigenetic signatures of active enhancers. Our mechanistic studies reveal that association of Mll2's CXXC domain with CpG-rich regions plays an instrumental role for chromatin targeting and subsequent implementation of H3K4me3. Although Mll2/COMPASS is required for H3K4me3 implementation on thousands of loci, generation of catalytically mutant MLL2/COMPASS demonstrated that H3K4me3 implemented by this enzyme was essential for expression of a subset of genes, including those functioning in the control of transcriptional programs during embryonic development. Our findings suggest that not all H3K4 trimethylations implemented by MLL2/COMPASS are functionally equivalent.
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