The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-beta)-activated gene transcription

摘要

Sma and Mad related (SMAD)-mediated Transforming Growth Factor 8 (TGF-beta) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteinssuch as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription.We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-/S-activated SMAD signaling. We immunoprecipitated PTIP and PA1 with all SMAD family members to identify the JCF-6 and not BMP-specific SMADs as interacting proteins. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-beta-specific genes to be regulated by the MLL4 complex, which links TGF-beta signaling to transcription regulation by the MLL4 methyltransferase complex.