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

Indira Bag, Shue Chen, Leah F. Rosin, Yang Chen, Chen-Yu Liu, Guo-Yun Yu and Elissa P. Lei ()
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Indira Bag: Nuclear Organization and Gene Expression Section
Shue Chen: Nuclear Organization and Gene Expression Section
Leah F. Rosin: Nuclear Organization and Gene Expression Section
Yang Chen: Nuclear Organization and Gene Expression Section
Chen-Yu Liu: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Guo-Yun Yu: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Elissa P. Lei: Nuclear Organization and Gene Expression Section

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24407-y

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