4u77
BTB domain from Drosophila CP190BTB domain from Drosophila CP190
Structural highlights
FunctionCP190_DROME Component of the gypsy chromatin insulator complex which is required for the function of the gypsy chromatin insulator and other endogenous chromatin insulators. Chromatin insulators are regulatory elements which establish independent domains of transcriptional activity within eukaryotic genomes. Insulators have two defining properties; they can block the communication between an enhancer and a promoter when placed between them and can also buffer transgenes from position effect variegation (PEV). Insulators are proposed to structure the chromatin fiber into independent domains of differing transcriptional potential by promoting the formation of distinct chromatin loops. This chromatin looping may involve the formation of insulator bodies, where homotypic interactions between individual subunits of the insulator complex could promote the clustering of widely spaced insulators at the nuclear periphery. Within the gypsy insulator complex, this protein may directly bind to insulator DNA at sites distinct from those recognized by su(Hw). Required during embryogenesis for axial expansion, an actin/myosin dependent process that distributes the dividing nuclei along the anterior-posterior axis of the syncytial embryo. Does not appear to play a crucial role in organizing centrosomal microtubules during mitosis.[1] [2] [3] Publication Abstract from PubMedChromatin insulators are genetic elements implicated in the organization of chromatin and the regulation of transcription. In Drosophila, different insulator types were characterized by their locus-specific composition of insulator proteins and co-factors. Insulators mediate specific long-range DNA contacts required for the three dimensional organization of the interphase nucleus and for transcription regulation, but the mechanisms underlying the formation of these contacts is currently unknown. Here, we investigate the molecular associations between different components of insulator complexes (BEAF32, CP190 and Chromator) by biochemical and biophysical means, and develop a novel single-molecule assay to determine what factors are necessary and essential for the formation of long-range DNA interactions. We show that BEAF32 is able to bind DNA specifically and with high affinity, but not to bridge long-range interactions (LRI). In contrast, we show that CP190 and Chromator are able to mediate LRI between specifically-bound BEAF32 nucleoprotein complexes in vitro. 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, and its C-terminal domain interacts with several insulator binding proteins. We propose a general model for insulator function in which BEAF32/dCTCF/Su(HW) provide DNA specificity (first layer proteins) whereas CP190/Chromator are responsible for the physical interactions required for long-range contacts (second layer). This network of organized, multi-layer interactions could explain the different activities of insulators as chromatin barriers, enhancer blockers, and transcriptional regulators, and suggest a general mechanism for how insulators may shape the organization of higher-order chromatin during cell division. Chromatin insulator factors involved in long-range DNA interactions and their role in the folding of the Drosophila genome.,Vogelmann J, Le Gall A, Dejardin S, Allemand F, Gamot A, Labesse G, Cuvier O, Negre N, Cohen-Gonsaud M, Margeat E, Nollmann M PLoS Genet. 2014 Aug 28;10(8):e1004544. doi: 10.1371/journal.pgen.1004544., eCollection 2014 Aug. PMID:25165871[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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