Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

Abstract

This is the first report that L(3)mbt-like 2 (L3MBTL2) specifically interacts with the histone deacetylase domain of histone deacetylase 3 (HDAC3) via its MBT domain. Here, we show that L3MBTL2 selectively interacts with HDAC3, but not other class I HDACs. An in vitro peptide-binding assay demonstrated the specific association of HDAC3 with methylated histone-K20 tail and L3MBTL2. Furthermore, depletion of HDAC3 resulted in a decrease of methylated K20-H4, as well as an increase in acetylated histone H3. Consequently, HDAC3 knock-down selectively suppressed L3MBTL2-mediated transcriptional repression. Taken together, our results reveal the concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression. Structured summaryMINT-7719975: L3MBTL2 (uniprotkb:Q969R5) and HDAC3 (uniprotkb:O15379) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7719941, MINT-7719921: L3MBTL2 (uniprotkb:Q969R5) binds (MI:0407) to HDAC3 (uniprotkb:O15379) by pull down (MI:0096)MINT-7719991: HDAC3 (uniprotkb:O15379) physically interacts (MI:0915) with L3MBTL2 (uniprotkb:Q969R5) by anti bait coimmunoprecipitation (MI:0006)MINT-7719958: L3MBTL2 (uniprotkb:Q969R5) physically interacts (MI:0915) with HDAC3 (uniprotkb:O15379) by anti tag coimmunoprecipitation (MI:0007)MINT-7719897: HDAC3 (uniprotkb:O15379) physically interacts (MI:0915) with L3MBTL2 (uniprotkb:Q969R5) by two hybrid (MI:0018)