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Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3


The histone deacetylase RPD3 can be targeted to certain genes through its interaction with DNA-binding regulatory proteins. RPD3 can then repress gene transcription1,2,3,4,5,6. In the yeast Saccharomyces cerevisiae, association of RPD3 with the transcriptional repressors SIN3 and UME6 results in repression of reporter genes containing the UME6-binding site3. RPD3 can deacetylate all histone H4 acetylation sites in cell extracts7. However, it is unknown how H4 proteins located at genes near UME6-binding sites are affected, nor whether the effect of RPD3 is localized to the promoter regions. Here we study the mechanism by which RPD3 represses gene activity by examining the acetylation state of histone proteins at UME6-regulated genes. We used antibodies specific for individual acetylation sites in H4 to immunoprecipitate chromatin fragments. A deletion of RPD3 or SIN3, but not of the related histone-deacetylase gene HDA1, results in increased acetylation of the lysine 5 residue of H4 in the promoters of the UME6-regulated INO1 (ref. 8), IME2 (ref. 3) and SPO13 (ref. 9) genes. As increased acetylation of this residue is not merely a consequence of gene transcription, acetylation of this site may be essential for regulating gene activity.

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Figure 1: Effect of RPD3 and HDA1 disruption on gene expression.
Figure 2: Effect of RPD3 disruption on acetylation of histone H4 at promoters of specific genes.
Figure 3: Effect of SIN3 disruption on acetylation of specific genes.
Figure 4: Effect of RPD3 disruption on histone acetylation next to the UME6-binding site (URS1).
Figure 5: Effect of galactose induction on transcription and H4 acetylation of GAL1.


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We thank S. Henry for discussions and R. Gaber for plasmid pMV117. This work was supported by Public Health Service grants from the NIH (to M.G.).

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Correspondence to Michael Grunstein.

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Rundlett, S., Carmen, A., Suka, N. et al. Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3. Nature 392, 831–835 (1998).

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