Hinge and Chromoshadow of HP1α Participate in Recognition of K9 Methylated Histone H3 in Nucleosomes

Mishima, Yuichiro; Watanabe, Mamoru; Kawakami, Toru; Jayasinghe, Chanika D.; Otani, Junji; Kikugawa, Yusuke; Shirakawa, Masahiro; Kimura, Hiroshi; Nishimura, Osamu; Aimoto, Saburo; Tsuji, Shoji; Suetake, Isao

doi:10.1016/j.jmb.2012.10.018

Cited by 46 publications

(83 citation statements)

References 29 publications

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“…Previous studies have shown that both human HP1α and the S. pombe HP1 protein, Swi6, display a lower specificity for the H3K9me3 mark in mononucleosomes than in H3-tail peptides, and that this specificity increases when assayed using nucleosome arrays (27,30). To further characterize the role of HP1α's N-terminal phosphorylation in its nucleosome binding, we examined HP1α's binding to a 12-mer nucleosome array with or without the H3Kc9me3 mark.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have indicated that two stretches of basic residues in the hinge region are critical for HP1's ability to bind DNA (30,32). However, the N-terminal and hinge regions are physically separated by the CD, and the functional interactions between these regions have yet to be defined.…”

Section: Resultsmentioning

confidence: 99%

“…Studies using reconstituted nucleosomes demonstrated that, although HP1 displays relatively lower binding specificity for H3K9me3-marked mononucleosome, the specificity increases when H3K9me3-marked oligonucleosomes are used as binding targets (27,30). Therefore, HP1's ability to bind H3K9me3-marked nucleosomes appears to be increased by its dimeric configuration, its higher-order intermolecular interactions or both (27).…”

Section: Introductionmentioning

confidence: 99%

“…HP1's DNA- or RNA-binding activities may also increase its affinity for H3K9me3 nucleosomes. Studies in various organisms have shown that HP1 binds DNA and RNA through its hinge region, without any particular sequence specificity, and that several stretches of basic residues in the hinge region contribute to this binding (30–35). Since HP1's heterochromatic localization in mammalian cells is sensitive to RNase treatment (35,36), nuclear RNA may guide HP1 to its target heterochromatin.…”

Section: Introductionmentioning

confidence: 99%

“…Since HP1's heterochromatic localization in mammalian cells is sensitive to RNase treatment (35,36), nuclear RNA may guide HP1 to its target heterochromatin. In vitro studies have demonstrated that DNA-binding activity associated with the hinge region contributes to HP1's preferential binding to nucleosomes with H3K9me3 (30) or with linker histones (32). …”

Section: Introductionmentioning

confidence: 99%

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N-terminal phosphorylation of HP1α increases its nucleosome-binding specificity

Nishibuchi¹,

Machida²,

Osakabe³

et al. 2014

Nucleic Acids Research

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Heterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that binds to lysine 9-methylated histone H3 (H3K9me), a hallmark of heterochromatin. Although HP1 phosphorylation has been described in several organisms, the biological implications of this modification remain largely elusive. Here we show that HP1's phosphorylation has a critical effect on its nucleosome binding properties. By in vitro phosphorylation assays and conventional chromatography, we demonstrated that casein kinase II (CK2) is the kinase primarily responsible for phosphorylating the N-terminus of human HP1α. Pull-down assays using in vitro-reconstituted nucleosomes showed that unmodified HP1α bound H3K9-methylated and H3K9-unmethylated nucleosomes with comparable affinity, whereas CK2-phosphorylated HP1α showed a high specificity for H3K9me3-modified nucleosomes. Electrophoretic mobility shift assays showed that CK2-mediated phosphorylation diminished HP1α's intrinsic DNA binding, which contributed to its H3K9me-independent nucleosome binding. CK2-mediated phosphorylation had a similar effect on the nucleosome-binding specificity of fly HP1a and S. pombe Swi6. These results suggested that HP1 phosphorylation has an evolutionarily conserved role in HP1's recognition of H3K9me-marked nucleosomes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

N-terminal phosphorylation of HP1α increases its nucleosome-binding specificity

Nishibuchi¹,

Machida²,

Osakabe³

et al. 2014

Nucleic Acids Research

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EPRSpectroscopy

2022

Analytical Techniques for the Elucidation of Protein Function

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Mind the Methyl: Methyllysine Binding Proteins in Epigenetic Regulation

et al. 2014

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Epigenetics is defined as the phenomenon of heritable phenotypic traits that are not governed by alteration of the genetic code. Major epigenetic control mechanisms include DNA methylation and post-translational modifications of histones, such as reversible histone acetylation and methylation of lysine residues. Methyllysine binding proteins recognize various levels of lysine methylation and mediate the signaling events that are induced by histone methylation. Therefore, they are also referred to as readers of the epigenetic code. In this article we review the current literature on the structure and biology of methyllysine binding proteins, especially with regard to their potential as drug targets. We also present the available inhibitors that block the interaction of methylated histones with their binding proteins.

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Hinge and Chromoshadow of HP1α Participate in Recognition of K9 Methylated Histone H3 in Nucleosomes

Cited by 46 publications

References 29 publications

N-terminal phosphorylation of HP1α increases its nucleosome-binding specificity

N-terminal phosphorylation of HP1α increases its nucleosome-binding specificity

EPRSpectroscopy

Mind the Methyl: Methyllysine Binding Proteins in Epigenetic Regulation

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