Nuclear Organization and Gene Expression Section, Bethesda, MD, USA.
Laboratory of Biochemistry and Genetics, Bethesda, MD, USA.
Nat Commun. 2021 Jul 7;12(1):4170. doi: 10.1038/s41467-021-24407-y.
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.
基因组组织受影响转录状态的力驱动，但转录和基因组结构之间的关系仍不清楚。在这里，我们在物理上鉴定了果蝇转录因子 Motif 1 结合蛋白（M1BP）与 gypsy 染色质绝缘子核心复合物相关联，包括普遍的绝缘子蛋白 CP190。M1BP 对于 gypsy 绝缘子的增强子阻断和屏障活性以及其适当的核定位是必需的。在全基因组范围内，M1BP 特异性地与含有 Motif 1 的启动子处的 CP190 共定位，这些启动子在拓扑关联域（TAD）边界处富集。M1BP 促进许多共享位点处的 CP190 染色质结合，反之亦然。这两个因素都促进了 TAD 边界附近的 Motif 1 依赖性基因表达和转录。最后，M1BP 的缺失降低了染色质可及性，并增加了 TAD 内和 TAD 间的局部基因组紧缩。我们的结果揭示了 CP190 和 M1BP 之间的物理和功能相互作用，以激活 TAD 边界处的转录，并介导染色质绝缘子依赖的基因组组织。
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