Chromatin-associated HMG-17 is a major regulator of homeodomain transcription factor activity modulated by Wnt/β-catenin signaling

Melanie Amen; Herbert M. Espinoza; Carol Cox; Xiaowen Liang; Jianbo Wang; Todd M. E. Link; Richard G. Brennan; James F. Martin; Brad A. Amendt

doi:10.1093/nar/gkm1047

Back

Chromatin-associated HMG-17 is a major regulator of homeodomain transcription factor activity modulated by Wnt/β-catenin signaling

Journal article

Open access

Peer reviewed

Chromatin-associated HMG-17 is a major regulator of homeodomain transcription factor activity modulated by Wnt/β-catenin signaling

Melanie Amen, Herbert M. Espinoza, Carol Cox, Xiaowen Liang, Jianbo Wang, Todd M. E. Link, Richard G. Brennan, James F. Martin and Brad A. Amendt

Nucleic acids research, Vol.36(2), pp.462-476

11/27/2007

DOI: 10.1093/nar/gkm1047

PMCID: PMC2241859

PMID: 18045789

Files and links (1)

url

https://doi.org/10.1093/nar/gkm1047View

Published (Version of record) Open Access

Abstract

Homeodomain (HD) transcriptional activities are tightly regulated during embryogenesis and require protein interactions for their spatial and temporal activation. The chromatin-associated high mobility group protein (HMG-17) is associated with transcriptionally active chromatin, however its role in regulating gene expression is unclear. This report reveals a unique strategy in which, HMG-17 acts as a molecular switch regulating HD transcriptional activity. The switch utilizes the Wnt/β-catenin signaling pathway and adds to the diverse functions of β-catenin. A high-affinity HMG-17 interaction with the PITX2 HD protein inhibits PITX2 DNA-binding activity. The HMG-17/PITX2 inactive complex is concentrated to specific nuclear regions primed for active transcription. β-Catenin forms a ternary complex with PITX2/HMG-17 to switch it from a repressor to an activator complex. Without β-catenin, HMG-17 can physically remove PITX2 from DNA to inhibit its transcriptional activity. The PITX2/HMG-17 regulatory complex acts independently of promoter targets and is a general mechanism for the control of HD transcriptional activity. HMG-17 is developmentally regulated and its unique role during embryogenesis is revealed by the early embryonic lethality of HMG-17 homozygous mice. This mechanism provides a new role for canonical Wnt/β-catenin signaling in regulating HD transcriptional activity during development using HMG-17 as a molecular switch.

Molecular Biology

Details

Title: Subtitle: Chromatin-associated HMG-17 is a major regulator of homeodomain transcription factor activity modulated by Wnt/β-catenin signaling
Creators: Melanie Amen - Texas A&M Health Science Center
Herbert M. Espinoza - Mitchell Institute
Carol Cox - University of Oklahoma
Xiaowen Liang - Mitchell Institute
Jianbo Wang - Mitchell Institute
Todd M. E. Link - Biochemistry and Molecular Biology
Richard G. Brennan - The University of Texas MD Anderson Cancer Center
James F. Martin - Mitchell Institute
Brad A. Amendt - Mitchell Institute
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.36(2), pp.462-476
DOI: 10.1093/nar/gkm1047
PMID: 18045789
PMCID: PMC2241859
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: Oxford University Press
Language: English
Date published: 11/27/2007
Academic Unit: Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984284332302771

Metrics

12 Record Views

40 Times Cited - Web of Science