Photobleaching studies reveal that a single amino acid polymorphism is responsible for the differential binding affinities of linker histone subtypes H1.1 and H1.5

Flanagan, Thomas W.; Files, Jacob K.; Casano, Kelsey Rose; George, Eric M.; Brown, David T.

doi:10.1242/bio.016733

Cited by 18 publications

(18 citation statements)

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“…The other potential reason for higher mobility of H1.X than H1.0 is their different GD affinities to nucleosomes because of a positive charge at position 73 in the GD of H1.X. Among the somatic linker histone variants other than H1.X, H1.1 moves most quickly (24,43). It was recently reported that a positive charge located around the border between the GD and CTD plays a critical role in the quick mobility of mouse H1.1 (43).…”

Section: Discussionmentioning

confidence: 99%

“…Among the somatic linker histone variants other than H1.X, H1.1 moves most quickly (24,43). It was recently reported that a positive charge located around the border between the GD and CTD plays a critical role in the quick mobility of mouse H1.1 (43). The corresponding amino acid residue in human H1.1 is not conserved, and this position is a serine (Ser115).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X

Okuwaki

Abé

Hisaoka

et al. 2016

Molecular and Cellular Biology

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Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo. Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones. Histones, including linker histones, are highly basic proteins that randomly bind to DNA. To maintain genomic integrity, DNA binding of histones should be strictly controlled. It has been established that random DNA binding of histones abrogates the sequential nucleosome assembly process (1). Histone chaperones directly bind to histones and transfer them to DNA to assemble the chromatin structure. In addition, histone chaperones have been suggested to play an important role in inhibiting the unfavorable DNA binding of histones (1). Our previous studies identified template activating factor I (TAF-I), nucleosome assembly protein 1 (NAP1), and nucleophosmin/B23 as factors involved in regulating the transcription and replication of adenovirus chromatin (2, 3). Recently, all three proteins, TAF-I, NAP1, and B23, were found to function as linker histone chaperones (4-7). A nucleolar protein, nucleolin (NCL), and prothymosin ␣ (ProT␣) were shown to regulate linker histone-chromatin binding (8-10).Linker histones are comprised of three regions: the N-terminal domain (NTD), central globular domain (GD), and C-terminal domain (CTD). The GDs of about 80 amino acids are able to reside on the DNA entry and exit sites of a nucleosome (11). Recent structural analysis of the GD of chicken linker histone H5 demonstrated that the GD makes contact with two extended DNA strands from the nucleosome and the nucleosome dyad (12). The CTD of linker histones are generally basic and rich in lysines, alanines, and prolines. The CTD plays a critical role in the condensation of DNA through its random DNA binding activity (13,14). The GD and CTD show distinct DNA binding activity (15), but neither is sufficient to stably associate with nu...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X

Okuwaki

Abé

Hisaoka

et al. 2016

Molecular and Cellular Biology

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“…It may differ from the final official version of record. different binding affinities of these two variants (Flanagan et al 2016). Lastly, it should be noted that, although changes in the C-terminal region of histones (such as those observed between mussel H2A.Z variants) are not likely to produce variations in nucleosomal stability, they still have the ability to modify the epigenetic profile of chromatin.…”

Section: Recombinant Expression Of Mussel H2az Variants and Analysismentioning

confidence: 99%

Characterization of mussel H2A.Z.2: a new H2A.Z variant preferentially expressed in germinal tissues fromMytilus

Rivera-Casas

González-Romero

Vizoso-Vazquez

et al. 2016

Biochem. Cell Biol.

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Histones are the fundamental constituents of the eukaryotic chromatin, facilitating the physical organization of DNA in chromosomes and participating in the regulation of its metabolism. The H2A family displays the largest number of variants among core histones, including the renowned H2A.X, macroH2A, H2A.B (Bbd), and H2A.Z. This latter variant is especially interesting because of its regulatory role and its differentiation into 2 functionally divergent variants (H2A.Z.1 and H2A.Z.2), further specializing the structure and function of vertebrate chromatin. In the present work we describe, for the first time, the presence of a second H2A.Z variant (H2A.Z.2) in the genome of a non-vertebrate animal, the mussel Mytilus. The molecular and evolutionary characterization of mussel H2A.Z.1 and H2A.Z.2 histones is consistent with their functional specialization, supported on sequence divergence at promoter and coding regions as well as on varying gene expression patterns. More precisely, the expression of H2A.Z.2 transcripts in gonadal tissue and its potential upregulation in response to genotoxic stress might be mirroring the specialization of this variant in DNA repair. Overall, the findings presented in this work complement recent reports describing the widespread presence of other histone variants across eukaryotes, supporting an ancestral origin and conserved role for histone variants in chromatin.

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“…This is consistent with biochemical evidence that the arginine binds more tightly to DNA than lysine, consistent with a more highly compacted chromatin in quiescent cells (Leng and Felsenfeld, 1966). Moreover, different H1 isotypes exhibit different motilities within live nuclei, which may be related to differential functions (Flanagan et al, 2016; Hendzel et al, 2004; Misteli et al, 2000; Stasevich et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

Linker histones: novel insights into structure-specific recognition of the nucleosome

Cutter

Hayes

2017

Biochem. Cell Biol.

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Linker histones (H1s) are a primary component of metazoan chromatin, fulfilling numerous functions, both in vitro and in vivo, including stabilizing wrapping of DNA around the nucleosome, promoting folding and assembly of higher order chromatin structures influencing nucleosome spacing on DNA and regulating specific gene expression. However, many molecular details of how H1 binds to nucleosomes and recognizes unique structural features on the nucleosome surface remain undefined. Numerous, confounding studies are complicated not only by experimental limitations, but the use of different linker histone isoforms and nucleosome constructions. This review summarizes the decades of research that has resulted in several models of H1 association with nucleosomes, and focuses on recent advances that suggest modes of binding may influence chromatin organization while also highlighting remaining questions.

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Photobleaching studies reveal that a single amino acid polymorphism is responsible for the differential binding affinities of linker histone subtypes H1.1 and H1.5

Cited by 18 publications

References 64 publications

Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X

Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X

Characterization of mussel H2A.Z.2: a new H2A.Z variant preferentially expressed in germinal tissues fromMytilus

Linker histones: novel insights into structure-specific recognition of the nucleosome

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