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Interactions among regulatory sequences such as enhancers, promoters and insulators give rise to a three-dimensional structure of the genetic material in the eukaryotic nucleus. We have used 5C and HiC to determine the nature of inter- and intra-chromosomal interactions in the Drosophila genome. The results suggest that each chromosome arm is an independent physical unit in terms of its interactions with the rest of the genome. Each chromosome folds into modules with a hierarchical organization. These modules comprise 80% of the genome, they are composed of different types of chromatin, they have a low gene density, and the genes are expressed at low levels, independent of their chromatin composition. Chromosome modules are separated by inter-module regions that comprise 20% of the genome. Inter-module regions have high gene density and comprise different chromatin types, but genes are expressed at higher levels than in chromosome modules. Inter-chromosome modules contain insulator proteins, which, together with RNA polymerase II, mediate interactions with other inter-chromosome modules. Chromosome modules also interact with each other but these interactions are not enriched in any known proteins. We are attempting to deconstruct this 3D structure into specific classes of interactions and determine their role in gene expression. In addition, we are exploring mechanisms by which organization can be regulated. In particular, parylation of insulator proteins appears to regulate interactions among these proteins and the establishment of a specific three-dimensional organization of the chromatin.
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Throwing transcription for a loop : the role of chromatin insulators in the 3D nucleus / Victor Corces.
Author:
Corces, Victor. National Institutes of Health (U.S.)
Publisher:
Abstract:
(CIT): Interactions among regulatory sequences such as enhancers, promoters and insulators give rise to a three-dimensional structure of the genetic material in the eukaryotic nucleus. We have used 5C and HiC to determine the nature of inter- and intra-chromosomal interactions in the Drosophila genome. The results suggest that each chromosome arm is an independent physical unit in terms of its interactions with the rest of the genome. Each chromosome folds into modules with a hierarchical organization. These modules comprise 80% of the genome, they are composed of different types of chromatin, they have a low gene density, and the genes are expressed at low levels, independent of their chromatin composition. Chromosome modules are separated by inter-module regions that comprise 20% of the genome. Inter-module regions have high gene density and comprise different chromatin types, but genes are expressed at higher levels than in chromosome modules. Inter-chromosome modules contain insulator proteins, which, together with RNA polymerase II, mediate interactions with other inter-chromosome modules. Chromosome modules also interact with each other but these interactions are not enriched in any known proteins. We are attempting to deconstruct this 3D structure into specific classes of interactions and determine their role in gene expression. In addition, we are exploring mechanisms by which organization can be regulated. In particular, parylation of insulator proteins appears to regulate interactions among these proteins and the establishment of a specific three-dimensional organization of the chromatin.
