THESIS
2013
iii leaves, iv-x, 33 pages : illustrations ; 30 cm
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...[
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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.
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