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. 2008 Jul 1;105(26):9000-5.
doi: 10.1073/pnas.0800057105. Epub 2008 Jun 24.

Acetylation in the Globular Core of Histone H3 on lysine-56 Promotes Chromatin Disassembly During Transcriptional Activation

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Free PMC article

Acetylation in the Globular Core of Histone H3 on lysine-56 Promotes Chromatin Disassembly During Transcriptional Activation

Stephanie K Williams et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Promoter chromatin disassembly is a widely used mechanism to regulate eukaryotic transcriptional induction. Delaying histone H3/H4 removal from the yeast PHO5 promoter also leads to delayed removal of histones H2A/H2B, suggesting a constant equilibrium of assembly and disassembly of H2A/H2B, whereas H3/H4 disassembly is the highly regulated step. Toward understanding how H3/H4 disassembly is regulated, we observe a drastic increase in the levels of histone H3 acetylated on lysine-56 (K56ac) during promoter chromatin disassembly. Indeed, promoter chromatin disassembly is driven by Rtt109 and Asf1-dependent acetylation of H3 K56. Conversely, promoter chromatin reassembly during transcriptional repression is accompanied by decreased levels of histone H3 acetylated on lysine-56, and a mutation that prevents K56 acetylation increases the rate of transcriptional repression. As such, H3 K56 acetylation drives chromatin toward the disassembled state during transcriptional activation, whereas loss of H3 K56 acetylation drives the chromatin toward the assembled state.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Removal of H3/H4 is the rate-limiting step during chromatin disassembly. (A) Schematic of the PHO5 promoter region. Lighter circles represent nucleosomes that are disassembled upon transcriptional activation. The bar indicates the region amplified in the ChIP analyses. (B) Asf1 is required for the normal kinetics of PHO5 activation. Acid phosphatase levels were measured in strains JLY096 (WT) and SKW043 (asf1Δ) at the indicated times after transfer to low-phosphate media. (C and D) Histone H3 and H2B-HA levels over the PHO5 promoter relative to the GAL1 control region in WT yeast (C) and in asf1Δ yeast (D), from the same time course as in B.
Fig. 2.
Fig. 2.
H3 K56ac at the activating PHO5 promoter depends on Asf1 and its interaction with H3/H4 dimers. (A) Acid phosphatase levels were measured in strains BY4741 (WT) and BY4741asf1Δ (asf1Δ) at the indicated times after transfer to low-phosphate media. (B) Histone H3 levels over the PHO5 promoter relative to the GAL1 control region. Samples were taken from the same time course as in A. (C) Histone H3 K56ac levels, normalized to H3 levels, over the PHO5 promoter relative to the GAL1 control region. Samples were taken from the same time course as in A and B. (D) Location of Y112 and R145 residues (orange) of Asf1 (purple) in complex with histone H3 (turquoise) and H4 (green), derived from ref. . (E) Histone H3 levels over the PHO5 promoter in strains SKW047 (WT) and SKW048 (asf1Δ), normalized as in Fig. 1. (F) Histone H3 K56ac levels, normalized to H3 levels, over the PHO5 promoter region normalized as in Fig. 1. Samples were taken from the same time course in D and E. Although these data are from one experiment, the findings were highly reproducible.
Fig. 3.
Fig. 3.
H3 K56ac is required for normal activation of PHO5 and promoter chromatin disassembly. (A) Acid phosphatase levels were measured in strains that are WT, asf1Δ, K56Q, K56Q asf1Δ, K56R, and K56R asf1Δ versions of MSY421 at the indicated times after transfer to low-phosphate media. (B) Histone H3 levels at the PHO5 promoter, as in Fig. 1. Samples were taken from the same time course as in A. (C) Phosphatase levels were measured in strains BY4741 (WT), BY4741rtt109Δ (rtt109Δ), and BY4741asf1Δ (asf1Δ) at the indicated times after transfer to low-phosphate media. (D) Histone H3 levels at the PHO5 promoter normalized as in Fig. 1. Samples were taken from the same time course as in C. (E) Histone H3 K56ac levels, normalized to H3 levels, over the PHO5 promoter normalized as in Fig. 1. Samples were taken from the same time course as in C. (F) Rtt109-TAP levels at the PHO5 UAS and ORF in strain ZGY925 at the indicated times after switch to low-phosphate conditions. “Sepharose at UAS” gives an indication of background due to DNA binding to the Sepharose alone. “HA at UAS” represents the ChIP with an HA antibody. All data were normalized to the signal obtained at the GAL1 promoter.
Fig. 4.
Fig. 4.
Loss of H3 K56ac promotes transcriptional repression. (A) Histone H3 levels over the PHO5 promoter relative to the GAL1 control region; addition of phosphate promotes repression. (B) H3 K56ac levels over the PHO5 promoter relative to the GAL1 control region. (C) Histone H3 K56ac levels, normalized to H3 levels, over the PHO5 promoter relative to the GAL1 control region. Samples were taken from the same time course in A–C. (D) Acid phosphatase levels were measured in strains that are WT, K56Q, and K56R versions of MSY421. (E) Model for the role of H3 K56 acetylation in promoter chromatin disassembly during transcriptional induction, and loss of K56 acetylation in chromatin reassembly during transcriptional repression.

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