UMass Chan Medical School Faculty Publications
Title
Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene
UMMS Affiliation
Department of Cell and Developmental Biology
Publication Date
2013-2
Document Type
Article
Subjects
Animals; Cell Line; Chromatin; Core Binding Factor Alpha 1 Subunit; Deoxyribonuclease I; Gene Expression Regulation; Helix-Loop-Helix Motifs; Histones; Mesoderm; Mice; Osteoblasts; Point Mutation; Promoter Regions, Genetic; Protein Interaction Domains and Motifs; Transcription Factor AP-1
Disciplines
Cell and Developmental Biology | Genetics and Genomics | Molecular Genetics
Abstract
Epigenetic mechanisms mediating expression of the Runt-related transcription factor Runx2 are critical for controlling its osteogenic activity during skeletal development. Here, we characterized bona fide regulatory elements within 120 kbp of the endogenous bone-related Runx2 promoter (P1) in osteoblasts by genomic DNase I footprinting and chromatin immuno-precipitations (ChIPs). We identified a ~10 kbp genomic domain spanning the P1 promoter that interacts with acetylated histones H3 and H4 reflecting an open chromatin conformation in MC3T3 osteoblasts. This large chromatin domain contains a single major DNaseI hypersensitive (DHS) region that defines a 0.4 kbp "basal core" promoter. This region encompasses two endogenous genomic protein/DNA interaction sites (i.e., footprints at Activating Protein 1 [AP1], E-box and Runx motifs). Helix-Loop-Helix (HLH)/E-box occupancy and presence of the DHS region persists in several mesenchymal cell types, but AP1 site occupancy occurs only during S phase when Runx2 expression is minimal. Point-mutation of the HLH/E box dramatically reduces basal promoter activity. Our results indicate that the Runx2 P1 promoter utilizes two stable principal protein/DNA interaction domains associated with AP1 and HLH factors. These sites function together with dynamic and developmentally responsive sites in a major DHS region to support epigenetic control of bone-specific transcription when osteoblasts transition into a quiescent or differentiated state.
DOI of Published Version
10.1002/jcp.22109
Source
J Cell Physiol. 2013 Feb;228(2):313-21. doi: 10.1002/jcp.22109. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Journal of cellular physiology
PubMed ID
22886425
Repository Citation
Hovhannisyan H, Zhang Y, Hassan MQ, Wu H, Glackin C, Lian JB, Stein JL, Montecino MA, Stein GS, Van Wijnen AJ. (2013). Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene. UMass Chan Medical School Faculty Publications. https://doi.org/10.1002/jcp.22109. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/193