The analysis of novel distal Cebpa enhancers and silencers using a transcriptional model reveals the complex regulatory logic of hematopoietic lineage specification.

ABSTRACT: C/EBPα plays an instructive role in the macrophage-neutrophil cell-fate decision and its expression is necessary for neutrophil development. How Cebpa itself is regulated in the myeloid lineage is not known. We decoded the cis-regulatory logic of Cebpa, and two other myeloid transcription factors, Egr1 and Egr2, using a combined experimental-computational approach. With a reporter design capable of detecting both distal enhancers and silencers, we analyzed 46 putative cis-regulatory modules (CRMs) in cells representing myeloid progenitors, and derived early macrophages or neutrophils. In addition to novel enhancers, this analysis revealed a surprisingly large number of silencers. We determined the regulatory roles of 15 potential transcriptional regulators by testing 32,768 alternative seq

SUBMITTER: Bertolino E 

PROVIDER: S-EPMC4878123 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature