A dual role of H4K16 acetylation in the establishment of yeast silent chromatin

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
The EMBO Journal (Impact Factor: 10.75). 06/2011; 30(13):2610-21. DOI: 10.1038/emboj.2011.170
Source: PubMed

ABSTRACT Discrete regions of the eukaryotic genome assume heritable chromatin structure that is refractory to transcription. In budding yeast, silent chromatin is characterized by the binding of the Silent Information Regulatory (Sir) proteins to unmodified nucleosomes. Using an in vitro reconstitution assay, which allows us to load Sir proteins onto arrays of regularly spaced nucleosomes, we have examined the impact of specific histone modifications on Sir protein binding and linker DNA accessibility. Two typical marks for active chromatin, H3K79(me) and H4K16(ac) decrease the affinity of Sir3 for chromatin, yet only H4K16(ac) affects chromatin structure, as measured by nuclease accessibility. Surprisingly, we found that the Sir2-4 subcomplex, unlike Sir3, has higher affinity for chromatin carrying H4K16(ac). NAD-dependent deacetylation of H4K16(ac) promotes binding of the SIR holocomplex but not of the Sir2-4 heterodimer. This function of H4K16(ac) cannot be substituted by H3K56(ac). We conclude that acetylated H4K16 has a dual role in silencing: it recruits Sir2-4 and repels Sir3. Moreover, the deacetylation of H4K16(ac) by Sir2 actively promotes the high-affinity binding of the SIR holocomplex.

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Available from: Stephanie Kueng, Jul 30, 2015
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    • "Although Sir2 itself has previously been implicated in H3K56 deacetylation, it is possible that alone it is not able to compensate for the loss of Hst3 and Hst4. In addition, its role in H3K56 deacetylation is controversial and there are several reports presenting conflicting data (Oppikofer et al. 2011; Xu et al. 2007; Yang et al. 2008). It has recently been shown that HDACs mediate the stability of heterochromatin through the suppression of histone turnover (Aygun et al. 2013) and given that H3K56ac is conducive to DNA unwrapping at the entry/exit site of the nucleosome, removal of this modification may facilitate this process by inducing a more closed conformation at these sites. "
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    • "First, the heterodimer formed between Sir4 and Sir2 catalyzes the NAD-dependent deacetylation of lysines in the histone H4 N-terminal tail. The deacetylation of histone H4 K16, in particular, generates a preferred binding site for Sir3 (Oppikofer et al. 2011), allowing Sir3 to bind and spread to the adjacent unacetylated nucleosomes (reviewed by Norris and Boeke 2010; Rusche et al. 2003). Sir3 appears to bind nucleosomal arrays in a stable, stoichiometric complex with Sir2 and Sir4 (Cubizolles et al. 2006), which renders linker DNA less accessible to transcription factors or other mediators of RNA pol II engagement at the transcriptional start site (Aparicio et al. 1991; Strahl-Bolsinger et al. 1997; Hecht and Grunstein 1999; Chen and Widom 2005; Martino et al. 2009). "
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    • "This raises the possibility that the chromatin environment , and specifically histone acetylation, more than the recruitment of silencing factors is required to regulate recombination and Pol II transcription at rDNA. The dominant role of histone acetylation at H4K16 in the establishment of yeast silent chromatin was recently highlighted (Oppikofer et al., 2011). "
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