The functional role of the CARM1-SNF5 complex and its associated HMT activity in transcriptional activation by thyroid hormone receptor

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Authors: Hyo-Kyoung Choi ; Kyung-Chul Choi ; Ho-Geun Yoon ; Kunhong Kim ; Kyung-Sup Kim ; Yong-Ho Ahn ; Seungjoo Haam ; Yoo-Hyun Lee ; Hee-Bum Kang ; So-Young Oh

MeSH: Chromosomal Proteins, Non-Histone/physiology* ; DNA-Binding Proteins/physiology* ; HeLa Cells ; Histone Methyltransferases ; Histone-Lysine N-Methyltransferase/metabolism* ; Histones/metabolism ; Humans ; Iodide Peroxidase/metabolism ; Methylation ; Promoter Regions, Genetic ; Protein Methyltransferases ; Protein-Arginine N-Methyltransferases/physiology* ; Receptors, Thyroid Hormone/physiology* ; SMARCB1 Protein ; Transcription Factors/physiology* ; Transcriptional Activation*

Abstract: We have investigated the function and mechanisms of the CARM1-SNF5 complex in T3-dependent transcriptional activation. Using specific small interfering RNAs (siRNA) to knock down coactivators in HeLa α2 cells, we found that coactivator associated arginine methyltransferase 1 (CARM1) and SWI/SNF complex component 5 (SNF5) are important for T3-dependent transcriptional activation. The CARM1- SWI/SNF chromatin remodeling complex serves as a mechanism for the rapid reversal of H3-K9 methylation. Importantly, siRNA treatment against CARM1 and/or SNF5 increased the recruitment of HMTase G9a to the type 1 deiodinase (D1) promoter even with T3. Knocking- down either CARM1 or SNF5 also inhibited the down- regulation of histone macroH2A, which is correlated with transcriptional activation. Finally, knocking down CARM1 and SNF5 by siRNA impaired the association of these coactivators to the D1 promoter, suggesting functional importance of CARM1- SNF5 complex in T3-dependent transcriptional activation.