Acetylation in the globular core of histone H3 on lysine-56 promotes chromatin disassembly during transcriptional activation

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.Asf1 ͉ K56 acetylation ͉ transcription T he packaging of DNA together with histone proteins into chromatin is essential for regulating all of the activities of the eukaryotic genome, including repair, replication, and gene expression. The chromatin structure dynamically changes to facilitate these processes and regulate access to the DNA sequence. For example, nucleosomes are disassembled from many eukaryotic promoters during transcriptional activation to provide access to the general transcription machinery (1). The histone H3/H4 chaperone known as Asf1 contributes to the disassembly of histones H3/H4 from multiple budding yeast promoters during transcriptional activation (2-4).Histone posttranslational modifications may also play an important role in regulating chromatin disassembly. Many of the best studied sites of histone posttranslational modifications map to the N-terminal tails of the histones that extend out from the globular core of the nucleosome and are unlikely to have a direct influence on the structure of the nucleosome. By contrast, the newly identified acetylation of lysine-56 within the globular core of histone H3 (H3 K56ac) (5, 6) is unique because it is predicted to break a DNA:histone interaction, potentially destabilizing the nucleosome. H3 K56 acetylation occurs predominantly on newly synthesized histones that are assembled into chromatin after DNA replication (6) and are rapidly deacetylated after S phase (7,8). Functionally, K56 acetylation promotes survival after the exposure of cells to genotoxic agents because of its role in stabilizing the replisome (6, 9). The histone acetyltransferase (HAT) responsible for acetylation of K56 on newly synthesized histones is Rtt109 (10-12) and needs either of two histone chaperones, Asf1 or Vps75, for enzymatic activity (13).Given the requirement for the histone chaperone Asf1 for H3 K56 acetylation and its role in chromatin disassembly from promoters during transcriptional activation, we investi...

Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips

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Transcription factor interaction with COMPASS-like complex regulates histone H3K4 trimethylation for specific gene expression in plants

“…Posttranslational modifications of histones directly or indirectly regulate chromatin state, and they therefore are important for gene expression and heterochromatin silencing (2)(3)(4). For example, acetylation in the globular core histone H3 enables recruitment of the SWI/SNF nucleosome remodeling complex to facilitate gene transcription in yeast (5,6). In contrast, histone H3 methylation does not affect chromatin structure per se, but interacts with additional factors such as the Complex Proteins Associated with Set1/Set1 Complex (COMPASS)/SET1C in yeast (7) or COMPASS-like complex in mammals (8), which contains three structural core components BRE2/Ash2, SWD3/WDR5, and SWD1/RbBP5, and H3K4 methyltransferases such as Set1 in yeast or MLL1 in mammals (8).…”

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

“…We did not observe an effect of nutrient-deprivation on global expression of these histone marks (Figure S4). Next, to evaluate whether nutrient deprivation may result in a more specific redistribution of chromatin marks, ChIP-sequencing was performed for histone marks associated with active transcription (H3K4me3 [24], H3K27ac [25], and H3K56ac [26]). Short-term nutrient deprivation resulted in alterations in all 3 histone marks (Figure 4(a)).…”