M1BP cooperates with CP190 to activate transcription at TAD borders and promote chromatin insulator activity

Abstract Genome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified Drosophila factor Motif 1 Binding Protein (M1BP) in physical association with gypsy chromatin insulator core complex, including universal protein CP190. M1BP required for enhancer-blocking barrier activities of as well its proper nuclear localization. Genome-wide, specifically colocalizes CP190 at 1-containing promoters, which are enriched topologically associating domain (TAD) borders. facilitates binding many shared sites vice versa. Both factors promote 1-dependent gene expression near TAD borders genome-wide. Finally, loss reduces accessibility increases both inter- intra-TAD local compaction. Our results reveal functional interaction to activate mediate insulator-dependent organization.