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Histone H4 lysine 12 acetylation regulates telomeric heterochromatin plasticity in Saccharomyces cerevisiae.

Zhou BO, Wang SS, Zhang Y, Fu XH, Dang W, Lenzmeier BA, Zhou JQ - PLoS Genet. (2011)

Bottom Line: Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12.H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination.Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show that histones are dynamically acetylated on H4K12 at telomeric heterochromatin, and this acetylation regulates several of the dynamic telomere properties. Using a de novo heterochromatin formation assay, we surprisingly found that acetylated H4K12 survived the formation of telomeric heterochromatin. Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12. H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination. Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity.

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Model for the regulation of telomeric heterochromatin plasticity by histone H4K12 acetylation.In wild-type cells where subtelomeric histone H4K12 is partially acetylated, heterochromatin structure is plastic and accessible to proteins, such as the RNA polymerase machinery and the telomerase machinery. In H4K12 deacetylated strain, heterochromatin becomes aberrantly condensed and less accessible to proteins, thereby inhibiting chromosomal processes.
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pgen-1001272-g008: Model for the regulation of telomeric heterochromatin plasticity by histone H4K12 acetylation.In wild-type cells where subtelomeric histone H4K12 is partially acetylated, heterochromatin structure is plastic and accessible to proteins, such as the RNA polymerase machinery and the telomerase machinery. In H4K12 deacetylated strain, heterochromatin becomes aberrantly condensed and less accessible to proteins, thereby inhibiting chromosomal processes.

Mentions: In conclusion, heterochromatin is known as a highly condensed chromatin domain that is transcriptionally silent [1]. However, pioneering studies have recently revealed the dynamic aspect of yeast heterochromatin [11]–[13], [15]. In this study, we have built on these pioneering studies and shown that the H4K12R mutation led to a more condensed telomeric heterochromatin structure (Figure 5) and more static telomere metabolism (Figure 4, Figure 5, Figure 6, Figure 7). Therefore, we propose that H4K12 provides a mechanism for yeast cells to maintain partial plasticity of their telomeric heterochromatin (Figure 8). Interestingly, histone H4K12 acetylation has also been observed at the chromocenter in fly [58]. Mst1, the orthologue of Esa1 in fission yeast, acetylates H3K4 at pericentric heterochromatin to regulate heterochromatin reassembly [59]. TIP60, the orthologue of NuA4 in mammals, physically interacts with Sirt1, the mammalian homologue of Sir2 [60], and associates with tri-methylated H3K9, a hallmark of heterochromatin [61]. Hence, it will be of great interest to determine if histone acetylation also plays a general role in heterochromatin dynamics in other eukaryotes.


Histone H4 lysine 12 acetylation regulates telomeric heterochromatin plasticity in Saccharomyces cerevisiae.

Zhou BO, Wang SS, Zhang Y, Fu XH, Dang W, Lenzmeier BA, Zhou JQ - PLoS Genet. (2011)

Model for the regulation of telomeric heterochromatin plasticity by histone H4K12 acetylation.In wild-type cells where subtelomeric histone H4K12 is partially acetylated, heterochromatin structure is plastic and accessible to proteins, such as the RNA polymerase machinery and the telomerase machinery. In H4K12 deacetylated strain, heterochromatin becomes aberrantly condensed and less accessible to proteins, thereby inhibiting chromosomal processes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3020936&req=5

pgen-1001272-g008: Model for the regulation of telomeric heterochromatin plasticity by histone H4K12 acetylation.In wild-type cells where subtelomeric histone H4K12 is partially acetylated, heterochromatin structure is plastic and accessible to proteins, such as the RNA polymerase machinery and the telomerase machinery. In H4K12 deacetylated strain, heterochromatin becomes aberrantly condensed and less accessible to proteins, thereby inhibiting chromosomal processes.
Mentions: In conclusion, heterochromatin is known as a highly condensed chromatin domain that is transcriptionally silent [1]. However, pioneering studies have recently revealed the dynamic aspect of yeast heterochromatin [11]–[13], [15]. In this study, we have built on these pioneering studies and shown that the H4K12R mutation led to a more condensed telomeric heterochromatin structure (Figure 5) and more static telomere metabolism (Figure 4, Figure 5, Figure 6, Figure 7). Therefore, we propose that H4K12 provides a mechanism for yeast cells to maintain partial plasticity of their telomeric heterochromatin (Figure 8). Interestingly, histone H4K12 acetylation has also been observed at the chromocenter in fly [58]. Mst1, the orthologue of Esa1 in fission yeast, acetylates H3K4 at pericentric heterochromatin to regulate heterochromatin reassembly [59]. TIP60, the orthologue of NuA4 in mammals, physically interacts with Sirt1, the mammalian homologue of Sir2 [60], and associates with tri-methylated H3K9, a hallmark of heterochromatin [61]. Hence, it will be of great interest to determine if histone acetylation also plays a general role in heterochromatin dynamics in other eukaryotes.

Bottom Line: Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12.H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination.Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show that histones are dynamically acetylated on H4K12 at telomeric heterochromatin, and this acetylation regulates several of the dynamic telomere properties. Using a de novo heterochromatin formation assay, we surprisingly found that acetylated H4K12 survived the formation of telomeric heterochromatin. Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12. H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination. Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity.

Show MeSH
Related in: MedlinePlus