Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our studies indicate that the regulatory factor for X-box (RFX) family proteins repress collagen alpha2(I) gene (COL1A2) expression (Xu, Y., Wang, L., Buttice, G., Sengupta, P. K., and Smith, B. D. (2003) J. Biol. Chem. 278, 49134-49144; Xu, Y., Wang, L., Buttice, G., Sengupta, P. K., and Smith, B. D. (2004) J. Biol. Chem. 279, 41319-41332). In this study, we examined the mechanism(s) underlying the repression of collagen gene by RFX proteins. Two members of the RFX family, RFX1 and RFX5, associate with distinct sets of co-repressors on the collagen transcription start site in vitro. RFX5 specifically interacts with histone deacetylase 2 (HDAC2) and the mammalian transcriptional repressor (mSin3B), whereas RFX1 preferably interacts with HDAC1 and mSin3A. HDAC2 cooperates with RFX5 to down-regulate collagen promoter activity, whereas HDAC1 enhances inhibition of collagen promoter activity by RFX1. Interferon-gamma promotes the recruitment of RFX5/HDAC2/mSin3B to the collagen transcription start site but decreases the occupancy by RFX1/mSin3A as manifested by chromatin immunoprecipitation assay. RFX1 binds to the methylated collagen sequence with much higher affinity than unmethylated sequence, recruiting more HDAC1 and mSin3A. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, which inhibits DNA methylation, reduces RFX1/HDAC1 binding to the collagen transcription start site in chromatin immunoprecipitation assays. Finally, both RFX1 and RFX5 are acetylated in vivo. Trichostatin A stimulates the acetylation of RFX proteins and activates the collagen promoter activity. Collectively, our data strongly indicate two separate pathways for RFX proteins to repress collagen gene expression as follows: one for RFX5/HDAC2 in interferon-gamma-mediated repression, and the other for RFX1/HDAC1 in methylation-mediated collagen silencing.
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PMID:Regulatory factor for X-box family proteins differentially interact with histone deacetylases to repress collagen alpha2(I) gene (COL1A2) expression. 1646 47