Early enhancer establishment and regulatory locus complexity shape transcriptional programs in hematopoietic differentiation Journal Article
| Authors: | González, A. J.; Setty, M.; Leslie, C. S. |
| Article Title: | Early enhancer establishment and regulatory locus complexity shape transcriptional programs in hematopoietic differentiation |
| 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. © 2015 Nature America, Inc. |
| Keywords: | human cell; nonhuman; animal cell; mouse; gene expression; embryo; cell fate; cell differentiation; b lymphocyte; cell lineage; rna; dna; transcription regulation; histone; chromatin immunoprecipitation; quantitative analysis; hematopoiesis; dna sequence; hematopoietic stem cell; rna sequence; deoxyribonuclease; enhancer region; regulatory sequence; histone modification; transcription factor pu 1; human; priority journal; article |
| Journal Title: | Nature Genetics |
| Volume: | 47 |
| Issue: | 11 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-11-01 |
| Start Page: | 1249 |
| End Page: | 1259 |
| Language: | English |
| DOI: | 10.1038/ng.3402 |
| PROVIDER: | scopus |
| PMCID: | PMC4626279 |
| PUBMED: | 26390058 |
| DOI/URL: | |
| Notes: | Export Date: 2 December 2015 -- Source: Scopus |
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