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PMID: 9858536 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mechanism of regulatory target selection by the SOX high-mobility-group domain proteins as revealed by comparison of SOX1/2/3 and SOX9.

Molecular and cellular biology ·Vol. 19 ·No. 1 ·1999-01-00 ·Pages 107-20

Kamachi Y, Cheah KS, Kondoh H

Abstract

SOX proteins bind similar DNA motifs through their high-mobility-group (HMG) domains, but their action is highly specific with respect to target genes and cell type. We investigated the mechanism of target selection by comparing SOX1/2/3, which activate delta-crystallin minimal enhancer DC5, with SOX9, which activates Col2a1 minimal enhancer COL2C2. These enhancers depend on both the SOX binding site and the binding site of a putative partner factor. The DC5 site was equally bound and bent by the HMG domains of SOX1/2 and SOX9. The activation domains of these SOX proteins mapped at the distal portions of the C-terminal domains were not cell specific and were independent of the partner factor. Chimeric proteins produced between SOX1 and SOX9 showed that to activate the DC5 enhancer, the C-terminal domain must be that of SOX1, although the HMG domains were replaceable. The SOX2-VP16 fusion protein, in which the activation domain of SOX2 was replaced by that of VP16, activated the DC5 enhancer still in a partner factor-dependent manner. The results argue that the proximal portion of the C-terminal domain of SOX1/2 specifically interacts with the partner factor, and this interaction determines the specificity of the SOX1/2 action. Essentially the same results were obtained in the converse experiments in which COL2C2 activation by SOX9 was analyzed, except that specificity of SOX9-partner factor interaction also involved the SOX9 HMG domain. The highly selective SOX-partner factor interactions presumably stabilize the DNA binding of the SOX proteins and provide the mechanism for regulatory target selection.

MeSH Terms
Animals Base Sequence Binding Sites Chick Embryo Collagen/genetics Crystallins/genetics DNA, Complementary DNA-Binding Proteins/genetics,metabolism Enhancer Elements, Genetic Gene Expression Regulation HMGB Proteins Herpes Simplex Virus Protein Vmw65/genetics,metabolism High Mobility Group Proteins/genetics,metabolism Molecular Sequence Data Nuclear Proteins/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism SOX9 Transcription Factor SOXB1 Transcription Factors SOXC Transcription Factors Transcription Factors/genetics,metabolism Transcriptional Activation
Chemicals
Crystallins DNA, Complementary DNA-Binding Proteins HMGB Proteins Herpes Simplex Virus Protein Vmw65 High Mobility Group Proteins Nuclear Proteins Recombinant Fusion Proteins SOX1 protein, human SOX9 Transcription Factor SOXB1 Transcription Factors SOXC Transcription Factors Sox11 protein, mouse Sox2 protein, mouse Sox3 protein, mouse Sox9 protein, mouse Transcription Factors Collagen
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kamachi Y
Institute for Molecular and Cellular Biology, Osaka University, Osaka 565-0871, Japan.
Cheah K S
Kondoh H
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.1.107
Published
1999-01-00
Pages
107-20
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC83870
Subset
IM
Databases
GENBANK
AB012236, AB012237
External Links
PubMed source DOI: 10.1128/MCB.19.1.107 PMC Full Text View journal details
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