Parallel but non-redundant roles of PaxBP1 and Carm1 in promoting the interaction between Pax7 and the H3K4 histone methyltransferase complex

Abstract

Pax7 is a key transcription factor that regulates muscle satellite cells development including lineage commitment, muscle progenitor cell proliferation. Pax7 activates its downstream target genes via recruitment of the H3K4 histone methyltransferase (HMT) complex. H3K4 tri-methylation is an epigenetic modification that is normally associated with gene activation. Our laboratory previously identified a novel protein PaxBP1 that can directly bind to Pax7 and serve as an adapter between Pax7 and the H3K4 HMT complex. Interestingly, Carm1, a protein arginine methyltransferase, was recently shown to directly methylate Pax7 on specific Arg residues, which promotes the interaction between Pax7 and MLL1/2, the catalytic component of the H3K4 HMT complex. Thus, questions arise regarding the relationships between PaxBP1 and CARM1 in facilitating Pax7 to recruit the H3K4 HMT complex. Here, using both the HMT enzymatic assays and protein binding assays, we demonstrated that both PaxBP1 and Carm1 are required for the Pax7-mediated HMT recruitment and enzymatic activity. Knockdown of PaxBP1 did not affect the binding of Pax7 with CARM1, while knockdown of Carm1 did not affect the binding of Pax7 with PaxBP1. This suggests that PaxBP1 and Carm1 have parallel but non-redundant roles in facilitating the Pax7-mediated recruitment of HMT. We are conducting more functional assays in muscle progenitor cells to further test this model.

Date of Award	2013
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology