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- Title
Early enhancer establishment and regulatory locus complexity shape transcriptional programs in hematopoietic differentiation.
- Authors
González, Alvaro J; Setty, Manu; Leslie, Christina S
- Abstract
We carried out an integrative analysis of enhancer landscape and gene expression dynamics during hematopoietic differentiation using DNase-seq, histone mark ChIP-seq and RNA sequencing to model how the early establishment of enhancers and regulatory locus complexity govern gene expression changes at cell state transitions. We found that high-complexity genes-those with a large total number of DNase-mapped enhancers across the lineage-differ architecturally and functionally from low-complexity genes, achieve larger expression changes and are enriched for both cell type-specific and transition enhancers, which are established in hematopoietic stem and progenitor cells and maintained in one differentiated cell fate but lost in others. We then developed a quantitative model to accurately predict gene expression changes from the DNA sequence content and lineage history of active enhancers. Our method suggests a new mechanistic role for PU.1 at transition peaks during B cell specification and can be used to correct assignments of enhancers to genes.
- Subjects
LOCUS (Genetics); HEMATOPOIETIC growth factors; GENE expression; MONOCYTES; GENETIC transcription
- Publication
Nature Genetics, 2015, Vol 47, Issue 11, p1249
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.3402