SUMOylation Regulates Super-Enhancers Through Transcription Factor TFAP2C Binding on Chromatin [ChIP-seq]

Genome wide localization of SUMO1 and SUMO2/3 proteins revealed an asscociation of SUMO proetins with active chromatin. SUMO proteins are enriched at super enhancers and enhancers and SUMOylation regulates a subset of these super enhancers. Super enhancers regulated by SUMOylation were enriched for transcription factor TFAP2C and SUMOylation negatively regulates TFAP2C localization to enhancers and super enhancers. Proteomics and ChIP-PCR at MYC SE suggests that chromatin bound TFAP2C recruits histone deacetylation complexes that increases upon SAE2 knockdown. Conversely, SUMOylation promoted TFAP2C asscociation with pre-mRNA splicing machinery components. Taken together, our study revealed a critical role of SUMOylation in chromatin modification through an AP-2 family of transcription factor, TFAP2C and a potential role of TFAP2C in pre-mRNA splicing. Genomic distribution of SUMO 1 and SUMO2/3 proteins and their association with chromatin marks H3K72Ac, H4K4me3, H3K27me3 and coactivator Med1 were probed. Chages to super enhancer components H3K27Ac and Med1 were analysed upon SAE2 kd (absence of SUMOylation). Genomic distrubution of TFAP2C in control and SUMOylation depleted cells were measured.