The Specificity and Topology of Chromatin Interaction Pathways in Yeast

Tineke L. Lenstra, Joris J. Benschop, Tae Soo Kim, Julia M. Schulze, Nathalie A.C.H. Brabers, Thanasis Margaritis, Loes A.L. van de Pasch, Sebastiaan A.A.C. van Heesch, Mariel O. Brok, Marian J.A. Groot Koerkamp, Cheuk W. Ko, Dik van Leenen, Katrin Sameith, Sander R. van Hooff, Philip Lijnzaad, Patrick Kemmeren, Thomas Hentrich, Michael S. Kobor, Stephen Buratowski, Frank C.P. Holstege

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

Packaging of DNA into chromatin has a profound impact on gene expression. To understand how changes in chromatin influence transcription, we analyzed 165 mutants of chromatin machinery components in Saccharomyces cerevisiae. mRNA expression patterns change in 80% of mutants, always with specific effects, even for loss of widespread histone marks. The data are assembled into a network of chromatin interaction pathways. The network is function based, has a branched, interconnected topology, and lacks strict one-to-one relationships between complexes. Chromatin pathways are not separate entities for different gene sets, but share many components. The study evaluates which interactions are important for which genes and predicts additional interactions, for example between Paf1C and Set3C, as well as a role for Mediator in subtelomeric silencing. The results indicate the presence of gene-dependent effects that go beyond context-dependent binding of chromatin factors and provide a framework for understanding how specificity is achieved through regulating chromatin.

Original languageEnglish
Pages (from-to)536-549
Number of pages14
JournalMolecular Cell
Volume42
Issue number4
DOIs
StatePublished - 20 May 2011

Bibliographical note

Funding Information:
We thank V. Geli and T. van Welsem for strains; and H.Th.M. Timmers, M. Vermeulen, F. van Leeuwen, and J.A. Lenstra for critical reading. Supported by the Netherlands Bioinformatics Centre (NBIC) and the Netherlands Organization of Scientific Research (NWO), grants 016108607, 81702015, 05071057, 91106009, 021002035 (T.L.L.), 86307007 (P.K.), and 70057407 (J.J.B.).

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