Chromatin Immunoprecipitation Indirect Peaks Highlight Long-Range Interactions of Insulator Proteins and Pol II Pausing
Chromatin Immunoprecipitation Indirect Peaks Highlight Long-Range Interactions of Insulator Proteins and Pol II Pausing
Eukaryotic chromosomes are partitioned into topologically associating domains (TADs) that are demarcated by distinct insulator-binding proteins (IBPs) in Drosophila. Whether IBPs regulate specific long-range contacts and how this may impact gene expression remains unclear. Here we identify "indirect peaks" of multiple IBPs that represent their distant sites of interactions through long-range contacts. Indirect peaks depend on protein-protein interactions among multiple IBPs and their common cofactors, including CP190, as confirmed by high-resolution analyses of long-range contacts. Mutant IBPs unable to interact with CP190 impair long-range contacts as well as the expression of hundreds of distant genes that are specifically flanked by indirect peaks. Regulation of distant genes strongly correlates with RNAPII pausing, highlighting how this key transcriptional stage may trap insulator-based long-range interactions. Our data illustrate how indirect peaks may decipher gene regulatory networks through specific long-range interactions.
- French National Centre for Scientific Research France
- National Institute of Health Pakistan
- École Nationale Vétérinaire de Toulouse France
- National Institutes of Health United States
- Massachusetts General Hospital United States
Physical borders, CCCTC-Binding Factor, Chromatin Immunoprecipitation, High-order chromatin organization, [SDV]Life Sciences [q-bio], 610, Chromosome, 616, Protein Interaction Mapping, Animals, Drosophila Proteins, Gene Regulatory Networks, Eye Proteins, Promoter Regions, Genetic, Molecular Biology, Binding Sites, Cell Biology, Transcription factories, [SDV] Life Sciences [q-bio], DNA-Binding Proteins, Repressor Proteins, Long-range interactions, Drosophila melanogaster, Gene Expression Regulation, RNA polymerase, Topolical domains, Mutation, Insulator, Insulator Elements, RNA Interference, RNA Polymerase II, Protein Binding, Transcription Factors
Physical borders, CCCTC-Binding Factor, Chromatin Immunoprecipitation, High-order chromatin organization, [SDV]Life Sciences [q-bio], 610, Chromosome, 616, Protein Interaction Mapping, Animals, Drosophila Proteins, Gene Regulatory Networks, Eye Proteins, Promoter Regions, Genetic, Molecular Biology, Binding Sites, Cell Biology, Transcription factories, [SDV] Life Sciences [q-bio], DNA-Binding Proteins, Repressor Proteins, Long-range interactions, Drosophila melanogaster, Gene Expression Regulation, RNA polymerase, Topolical domains, Mutation, Insulator, Insulator Elements, RNA Interference, RNA Polymerase II, Protein Binding, Transcription Factors
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