Chromatin Insulator Function and Nuclear Organization

染色质绝缘体功能和核组织

基本信息

批准号：
10248119
负责人：
Elissa Lei
金额：
$ 169.58万
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10248119
关键词：
Acute T Cell Leukemia Affect Architecture Beckwith-Wiedemann Syndrome Binding Binding Proteins Binding Sites Biochemical Biological Models Caliber Cell Nucleus Chromatin Complex DNA DNA-Binding Proteins Defect Development Disease Drosophila genus Enhancers Environment Erythropoiesis Gene Expression Genes Genetic Genetic Transcription Genome Glioma Gypsies H19 gene Homeobox Genes IGF2 gene Immunoprecipitation Location Mediating Messenger RNA Nephroblastoma Neurons Nuclear Nuclear Matrix Oncogene Activation Proteins RNA RNA Binding RNA Recognition Motif RNA-Binding Proteins Regulation Role Site Structure Tissues Transcriptional Activation Transcriptional Regulation Untranslated RNA Zinc Fingers beta Globin cell type chromatin protein cofactor deep sequencing genome-wide imprint mutant novel programs promoter protein complex scaffold spatial relationship transcription factor

项目摘要

The transcription factor M1BP cooperates with CP190 to activate transcription at TAD borders and promote chromatin insulator activity Organization of the genome is driven by forces affecting transcriptional state, but the relationship between transcription and the machinery controlling 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 is required for CP190 chromatin binding at many shared sites, and CP190 also affects M1BP chromatin association. Importantly, both factors are required for Motif 1-dependent gene expression and to promote transcriptional activation near TAD borders genome-wide. Our results reveal physical and functional interaction between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization.

转录因子M1BP与CP190合作，以激活TAD边界的转录并促进染色质绝缘子活性基因组的组织是由影响转录状态的力驱动的，但是转录与控制基因组结构的机械之间的关系尚不清楚。在这里，我们确定了果蝇转录因子基序1结合蛋白（M1bp）与吉普赛染色质绝缘子核心复合物（包括通用绝缘体蛋白CP190）的物理关联。 M1BP是吉普赛绝缘子的增强障碍物和障碍活动所必需的，以及其适当的核定位。全基因组，M1BP在含1个含1个启动子的CP190中特异性地共定位，这些启动子在拓扑结构域（TAD）边界富集。在许多共享位点，CP190染色质结合需要M1BP，CP190也会影响M1BP染色质关联。重要的是，基序1依赖性基因表达并促进TAD范围内基因组附近的转录激活所必需的这两个因素。我们的结果揭示了CP190和M1BP之间的身体和功能相互作用，以激活TAD边界的转录并介导染色质绝缘子依赖性基因组组织。