Chromatin Insulator Factors Involved in Long-Range DNA Interactions and Their Role in the Folding of the Drosophila Genome

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Chromatin insulators mediate specific long-range DNA interactions required for the three dimensional organization of the interphase nucleus and for transcription regulation, but the mechanisms underlying the formation of these interactions is currently unknown. In this manuscript, we investigate the molecular associations between different protein components of insulators (BEAF32, CP190 and Chromator) by biochemical and biophysical means, and develop a novel biophysical assay to determine what factors are necessary and essential for the formation of long-range DNA interactions (LRI). Importantly, we show that CP190 and Chromator are able to mediate LRIs between specifically-bound BEAF32 nucleoprotein complexes. This ability of CP190 and Chromator to establish LRI requires specific contacts between BEAF32 and their C-terminal domains, and dimerization through their N-terminal domains. In particular, the BTB/POZ domains of CP190 form a strict homodimer. We propose a general model for insulator function in which BEAF32/dCTCF/Su(HW) provide DNA specificity, whereas CP190/Chromator are responsible for the physical interactions required for long-range contacts. This network of organized, multi-layer interactions could explain the different activities of insulators, and suggest a general mechanism for how insulators may shape the organization of higher-order chromatin during cell division.

Vyšlo v časopise: Chromatin Insulator Factors Involved in Long-Range DNA Interactions and Their Role in the Folding of the Drosophila Genome. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004544
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004544

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