Abstract
The organization of chromatin into higher order structures is essential for chromosome segregation, the repair of DNA-damage, and the regulation of gene expression. Using Micro-C XL to detect chromosomal interactions, we observed the pervasive presence of cohesin-dependent loops with defined positions throughout the genome of budding yeast, as seen in mammalian cells. In early S phase, cohesin stably binds to cohesin associated regions (CARs) genome-wide. Subsequently, positioned loops accumulate with CARs at the bases of the loops. Cohesin regulators Wpl1 and Pds5 alter the levels and distribution of cohesin at CARs, changing the pattern of positioned loops. From these observations, we propose that cohesin with loop extrusion activity is stopped by preexisting CAR-bound cohesins, generating positioned loops. The patterns of loops observed in a population of wild-type and mutant cells can be explained by this mechanism, coupled with a heterogeneous residency of cohesin at CARs in individual cells.
Highlights
The genome is organized into three-dimensional structures that are essential for the correct segregation of chromosomes, the efficient repair of DNA damage, and the regulation of gene transcription
The paired reads from the chimeric sequences gave the coordinates of nucleosomes that were contacting in vivo
One feature of our study is the remarkable correlation between the anchors of positioned loops and cohesin associated regions (CARs)
Summary
The genome is organized into three-dimensional structures that are essential for the correct segregation of chromosomes, the efficient repair of DNA damage, and the regulation of gene transcription. These methods showed in mammalian cells the existence of chromatin loops at specific loci (Deng et al, 2012; Palstra et al, 2003; Tolhuis et al, 2002). The existence of these loops has inspired several outstanding questions, including what are the molecular mechanisms that drive the formation of loops, their genome distribution, their frequency in a population of cells, and their biological function(s)
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