A DNA Contact Map for the Mouse Runx1 Gene Identifies Novel Haematopoietic Enhancers. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Marsman, Judith; Thomas, Amarni; Osato, Motomi; O'Sullivan, Justin; Horsfield, Julia
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 11
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-13748-8
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract The transcription factor Runx1 is essential for definitive haematopoiesis, and theRUNX1 gene is frequently translocated or mutated in leukaemia.Runx1 is transcribed from two promoters, P1 and P2, to give rise to different protein isoforms. Although the expression of Runx1 must be tightly regulated for normal blood development, the mechanisms that regulateRunx1 isoform expression during haematopoiesis remain poorly understood. Gene regulatory elements located in non-coding DNA are likely to be important forRunx1 transcription. Here we use circular chromosome conformation capture sequencing to identify DNA interactions with the P1 and P2 promoters ofRunx1, and the previously identified +24 enhancer, in the mouse multipotent haematopoietic progenitor cell line HPC-7. The active promoter, P1, interacts with nine non-coding regions that are occupied by transcription factors within a 1 Mb topologically associated domain. Eight of nine regions function as blood-specific enhancers in zebrafish, of which two were previously shown to harbour blood-specific enhancer activity in mice. Interestingly, the +24 enhancer interacted with multiple distant regions on chromosome 16, suggesting it may regulate the expression of additional genes. TheRunx1 DNA contact map identifies connections with multiple novel and known haematopoietic enhancers that are likely to be involved in regulatingRunx1 expression in haematopoietic progenitor cells.