PUBLICATION
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.
- ID
- ZDB-PUB-171019-8
- Date
- 2017
- Source
- Scientific Reports 7: 13347 (Journal)
- Registered Authors
- Horsfield, Jules
- Keywords
- none
- MeSH Terms
-
- Animals
- Chromatin/genetics
- Chromatin/metabolism
- Chromatin Immunoprecipitation
- Core Binding Factor Alpha 2 Subunit/genetics*
- Core Binding Factor Alpha 2 Subunit/metabolism
- Enhancer Elements, Genetic
- Gene Expression Regulation, Developmental
- Genes, Reporter
- Genetic Loci
- Hematopoiesis/genetics*
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism*
- High-Throughput Nucleotide Sequencing
- Mice
- Models, Biological
- Phenotype
- Promoter Regions, Genetic
- Protein Binding
- PubMed
- 29042628 Full text @ Sci. Rep.
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. 7:13347.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping