Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2

Evan Diamond; Melanie Amen; Qiaoyan Hu; Herbert M. Espinoza; Brad A. Amendt

doi:10.1093/nar/gkl689

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Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2

Journal article

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Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2

Evan Diamond, Melanie Amen, Qiaoyan Hu, Herbert M. Espinoza and Brad A. Amendt

Nucleic acids research, Vol.34(20), pp.5951-5965

11/01/2006

DOI: 10.1093/nar/gkl689

PMCID: PMC1635299

PMID: 17068080

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Abstract

Dlx2, Lymphoid Enhancer Factor (Lef-1) and Msx2 transcription factors are required for several developmental processes. To understand the control of gene expression by these factors, chromatin immunoprecipitation (ChIP) assays identified Msx2 as a downstream target of Dlx2 and Lef-1. Dlx2 activates the Msx2 promoter in several cell lines and binds DNA as a monomer and dimer. A Lef-1 beta-catenin-dependent isoform minimally activates the Msx2 promoter and a Lef-1 beta-catenin-independent isoform is inactive, however co-expression of Dlx2 and both Lef-1 isoforms synergistically activate the Msx2 promoter. Co-immunoprecipitation and protein pull-down experiments demonstrate Lef-1 physically interacts with Dlx2. Deletion analyses of the Lef-1 protein reveal specific regions required for synergism with Dlx2. The Lef-1 beta-catenin binding domain (beta DB) is not required for its interaction with Dlx2. Msx2 can auto-regulate its promoter and repress Dlx2 activation. Msx2 repression of Dlx2 activation is dose-specific and both bind a common DNA-binding element. These transcriptional mechanisms correlate with the temporal and spatial expression of these factors and may provide a mechanism for the control of several developmental processes. We demonstrate new transcriptional activities for Dlx2, Msx2 and Lef-1 through protein interactions and identification of downstream targets.

Biochemistry & Molecular Biology

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2
Creators: Evan Diamond - Texas A&M Health Science Center
Melanie Amen
Qiaoyan Hu
Herbert M. Espinoza
Brad A. Amendt
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.34(20), pp.5951-5965
DOI: 10.1093/nar/gkl689
PMID: 17068080
PMCID: PMC1635299
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: Oxford Univ Press
Number of pages: 15
Grant note: R01 DE013941; DE13941 / NIDCR NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) P30 ES009106; ES09106 / NIEHS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R01DE013941 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) P30ES009106 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
Language: English
Date published: 11/01/2006
Academic Unit: Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984284353402771

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