A chromatin-mediated mechanism for specification of conditional transcription factor targets

ABSTRACT Organisms respond to changes in their environment, and many such responses are initiated at the level of gene transcription. Here, we provide evidence for a previously undiscovered

mechanism for directing transcriptional regulators to new binding targets in response to an environmental change. We show that repressor-activator protein 1 (Rap1), a master regulator of

yeast metabolism, binds to an expanded target set after glucose depletion despite decreasing protein levels and no evidence of posttranslational modification. Computational analysis predicts

that proteins capable of recruiting the chromatin regulator Tup1 act to restrict the binding distribution of Rap1 in the presence of glucose. Deletion of the gene(s) encoding Tup1,

recruiters of Tup1 or chromatin regulators recruited by Tup1 cause Rap1 to bind specifically and inappropriately to low-glucose targets. These data, combined with whole-genome measurements

of nucleosome occupancy and Tup1 distribution, provide evidence for a mechanism of dynamic target specification that coordinates the genome-wide distribution of intermediate-affinity DNA

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FACTOR SENSITIVITY TO CHROMATIN Article 12 July 2022 ADAPTIVE PARTITIONING OF A GENE LOCUS TO THE NUCLEAR ENVELOPE IN _SACCHAROMYCES CEREVISIAE_ IS DRIVEN BY POLYMER-POLYMER PHASE

SEPARATION Article Open access 28 February 2023 THE YEAST GENOME IS GLOBALLY ACCESSIBLE IN LIVING CELLS Article Open access 25 November 2024 ACCESSION CODES ACCESSIONS GENE EXPRESSION

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University of California, San Francisco) for providing a strain. This work was supported by US National Institutes of Health grant HG002989 to M.J.B. and GM072518 to J.D.L. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Department of Biology and the Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, USA

Michael J Buck & Jason D Lieb Authors * Michael J Buck View author publications You can also search for this author inPubMed Google Scholar * Jason D Lieb View author publications You

can also search for this author inPubMed Google Scholar CONTRIBUTIONS This study was designed by M.J.B. and J.D.L. M.J.B conducted the experiments and data analysis. M.J.B. and J.D.L. wrote

the paper. CORRESPONDING AUTHOR Correspondence to Jason D Lieb. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION

SUPPLEMENTARY FIG. 1 Rap1 protein and mRNA levels decrease as glucose is depleted. (PDF 462 kb) SUPPLEMENTARY FIG. 2 Confirmation of ChIP-chip results by PCR. (PDF 1488 kb) SUPPLEMENTARY

FIG. 3 Confirmation of ChIP-chip results at the SGA1 locus. (PDF 924 kb) SUPPLEMENTARY FIG. 4 Computational screens predict the involvement of Tup1-Ssn6 proteins in blocking Rap1 binding.

(PDF 290 kb) SUPPLEMENTARY FIG. 5 Rap1 binding and glycolysis. (PDF 372 kb) SUPPLEMENTARY TABLE 1 ChIP-chip experiments. (PDF 53 kb) SUPPLEMENTARY TABLE 2 Rap1 binding targets. (XLS 71 kb)

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Buck, M., Lieb, J. A chromatin-mediated mechanism for specification of conditional transcription factor

targets. _Nat Genet_ 38, 1446–1451 (2006). https://doi.org/10.1038/ng1917 Download citation * Received: 11 September 2006 * Accepted: 04 October 2006 * Published: 12 November 2006 * Issue

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