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

• Published in: Nature communications Vol. 12; no. 1; p. 4170
• Main Authors: Bag, Indira, Chen, Shue, Rosin, Leah F., Chen, Yang, Liu, Chen-Yu, Yu, Guo-Yun, Lei, Elissa P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 07.07.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Borders; Chromatin; Domains; Drosophila; Fruit flies; Gene expression; Genomes; Insects; Localization; Proteins; Transcription factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24407-y

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