PARP1 and DNMT1 interact with the DUX4 promoter in FSHD myoblasts, suggesting a role in the epigenetic regulation of DUX4 expression in Facioscapulohumeral Muscular Dystrophy.
Hypothesis-generating for PARP1-DNMT1 targeting in FSHD; leaves open any clinical role pending in vivo validation.
OBJECTIVE: The goal of the study is to identity proteins, which interact with the promoter region of double homeobox protein 4 (DUX4) gene known to be causative for the autosomal dominant disorder Facioscapulohumeral Muscular Dystrophy (FSHD). METHODS: We performed a DNA pull down assay coupled with mass spectrometry analysis to identify proteins that interact with a DUX4 promoter probe in Rhabdomyosarcomca (RD) cells. We selected the top ranked protein poly (ADP-ribose) polymerase 1 (PARP1) from our mass spectrometry data for further ChIP-qPCR validation using patients' myoblasts. We then treated FSHD myoblasts with PARP1 inhibitors to investigate the role of PARP1 in the FSHD myoblasts. RESULTS: (2.2 fold, p<0.05) in the FSHD myoblasts. We further showed that DNA methyltransferase 1 (DNMT1), a gene regulated by PARP1 was also enriched at the DUX4 promoter in RD cells through immunoblotting (2-fold, p<0.01) and immortalized FSHD myoblasts (42-fold, p<0.01) but not control myoblasts through ChIP qPCR. CONCLUSION: expression in FSHD.
No takes yet. Share an insight, caveat, or question.
Sharma et al. (2016) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: