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Cohesinopathy mutations disrupt the subnuclear organization of chromatin

¹ Stowers Institute for Medical Research, Kansas City, MO 64110
² Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160
³ Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208

Correspondence to Jennifer L.Gerton: jeg{at}stowers.org

In Saccharomyces cerevisiae, chromatin is spatially organized within the nucleus with centromeres clustering near the spindle pole body, telomeres clustering into foci at the nuclear periphery, recombinant DNA repeats localizing within a single nucleolus, and transfer RNA (tRNA) genes present in an adjacent cluster. Furthermore, certain genes relocalize from the nuclear interior to the periphery upon transcriptional activation. The molecular mechanisms responsible for the organization of the genome are not well understood. We find that evolutionarily conserved proteins in the cohesin network play an important role in the subnuclear organization of chromatin. Mutations that cause human cohesinopathies had little effect on chromosome cohesion, centromere clustering, or viability when expressed in yeast. However, two mutations in particular lead to defects in (a) GAL2 transcription and recruitment to the nuclear periphery, (b) condensation of mitotic chromosomes, (c) nucleolar morphology, and (d) tRNA gene–mediated silencing and clustering of tRNA genes. We propose that the cohesin network affects gene regulation by facilitating the subnuclear organization of chromatin.

Abbreviations used in this paper: CdLS, Cornelia de Lange syndrome; ChIP, chromatin immunoprecipitation; PSCS, precocious sister chromatid separation; qPCR, quantitative PCR; rDNA, ribosomal DNA; tgm, tRNA gene mediated; WT, wild type.

© 2009 Gard et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• Short, B. (2009). Cohesin pathway makes the necessary arrangements. JCB 187: 444-444 [Full Text]  

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