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Publication : Mint represses transactivation of the type II collagen gene enhancer through interaction with alpha A-crystallin-binding protein 1.

First Author  Yang X Year  2005
Journal  J Biol Chem Volume  280
Issue  19 Pages  18710-6
PubMed ID  15778499 Mgi Jnum  J:99923
Mgi Id  MGI:3584225 Doi  10.1074/jbc.M500859200
Citation  Yang X, et al. (2005) Mint represses transactivation of the type II collagen gene enhancer through interaction with alpha A-crystallin-binding protein 1. J Biol Chem 280(19):18710-6
abstractText  Collagen type II is an extracellular matrix protein important for cartilage and bone formation, and its expression is controlled by multiple cis- and trans-acting elements, including the zinc finger transcription factor alpha A-crystallin-binding protein 1 (CRYBP1). Here we show that MSX2-interacting nuclear target protein (MINT), a conserved transcriptional repressor, associates with CRYBP1 and negatively regulates the transactivation of the collagen type II gene (Col2a1) enhancer. We identified CRYBP1 as a binding partner of MINT by screening a mouse embryonic cDNA library using the yeast two-hybrid system. We demonstrated that the C terminus of MINT interacts with the C terminus of CRYBP1 using the mammalian cell two-hybrid assay, glutathione S-transferase pull-down, and co-immunoprecipitation analyses. Furthermore, MINT and CRYBP1 form a complex on the Col2a1 enhancer, as shown by chromatin immunoprecipitation and gel shift assays. In the presence of CRYBP1, overexpression of MINT or its C-terminal fragment in cells repressed a reporter construct driven by the Col2a1 enhancer elements. This transcription repression is dependent on histone deacetylase, the main co-repressor recruited by MINT. The present study shows that MINT is involved in CRYBP1-mediated Col2a1 gene repression and may play a role in regulation of cartilage development.
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