Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-017-13748-8
Title: A DNA contact map for the mouse runx1 gene identifies novel haematopoietic enhancers
Authors: Marsman, J
Thomas, A
Osato, M 
O'sullivan, J.M
Horsfield, J.A
Keywords: protein binding
RUNX1 protein, human
transcription factor RUNX1
animal
biological model
chromatin
chromatin immunoprecipitation
cytology
enhancer region
gene expression regulation
gene locus
genetics
hematopoiesis
hematopoietic stem cell
high throughput sequencing
metabolism
mouse
phenotype
promoter region
reporter gene
Animals
Chromatin
Chromatin Immunoprecipitation
Core Binding Factor Alpha 2 Subunit
Enhancer Elements, Genetic
Gene Expression Regulation, Developmental
Genes, Reporter
Genetic Loci
Hematopoiesis
Hematopoietic Stem Cells
High-Throughput Nucleotide Sequencing
Mice
Models, Biological
Phenotype
Promoter Regions, Genetic
Protein Binding
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Marsman, J, Thomas, A, Osato, M, O'sullivan, J.M, Horsfield, J.A (2017). A DNA contact map for the mouse runx1 gene identifies novel haematopoietic enhancers. Scientific Reports 7 (1) : 13347. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-13748-8
Rights: Attribution 4.0 International
Abstract: The transcription factor Runx1 is essential for definitive haematopoiesis, and the RUNX1 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 regulate Runx1 isoform expression during haematopoiesis remain poorly understood. Gene regulatory elements located in non-coding DNA are likely to be important for Runx1 transcription. Here we use circular chromosome conformation capture sequencing to identify DNA interactions with the P1 and P2 promoters of Runx1, 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. The Runx1 DNA contact map identifies connections with multiple novel and known haematopoietic enhancers that are likely to be involved in regulating Runx1 expression in haematopoietic progenitor cells. © 2017 The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/178568
ISSN: 2045-2322
DOI: 10.1038/s41598-017-13748-8
Rights: Attribution 4.0 International
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