Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length

Woodcock, Christopher L.; Skoultchi, Arthur I.; Fan, Yuhong

doi:10.1007/s10577-005-1024-3

Cited by 414 publications

(421 citation statements)

References 81 publications

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“…However, LH is present at various lower levels in proliferating cells (31) and is not required for metaphase chromatin condensation (30,37). The above-cited studies are consistent with our finding that the pattern of internucleosomal interactions in metaphase chromosomes is typical of chromatin without LHs (Fig.…”

Section: Discussionsupporting

confidence: 91%

“…Linker histone H1 is nonessential for metaphase chromosome condensation (30) and the majority of proliferating cells contain different substoichiometric levels of linker histone (31). Therefore, folding of the 191-and 209-bp chromatin fibers was also simulated in the presence of stoichiometric (one LH per nucleosome) and substoichiometric (one LH per two nucleosomes) linker histone.…”

Section: Mesoscale Modeling Reveals Hierarchically Folded Loops In Chmentioning

confidence: 99%

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Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Grigoryev

Bascom

Buckwalter

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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174

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The architecture of higher-order chromatin in eukaryotic cell nuclei is largely unknown. Here, we use electron microscopy-assisted nucleosome interaction capture (EMANIC) cross-linking experiments in combination with mesoscale chromatin modeling of 96-nucleosome arrays to investigate the internal organization of condensed chromatin in interphase cell nuclei and metaphase chromosomes at nucleosomal resolution. The combined data suggest a novel hierarchical looping model for chromatin higher-order folding, similar to rope flaking used in mountain climbing and rappelling. Not only does such packing help to avoid tangling and self-crossing, it also facilitates rope unraveling. Hierarchical looping is characterized by an increased frequency of higher-order internucleosome contacts for metaphase chromosomes compared with chromatin fibers in vitro and interphase chromatin, with preservation of a dominant two-start zigzag organization associated with the 30-nm fiber. Moreover, the strong dependence of looping on linker histone concentration suggests a hierarchical self-association mechanism of relaxed nucleosome zigzag chains rather than longitudinal compaction as seen in 30-nm fibers. Specifically, concentrations lower than one linker histone per nucleosome promote self-associations and formation of these looped networks of zigzag fibers. The combined experimental and modeling evidence for condensed metaphase chromatin as hierarchical loops and bundles of relaxed zigzag nucleosomal chains rather than randomly coiled threads or straight and stiff helical fibers reconciles aspects of other models for higher-order chromatin structure; it constitutes not only an efficient storage form for the genomic material, consistent with other genome-wide chromosome conformation studies that emphasize looping, but also a convenient organization for local DNA unraveling and genome access. chromatin higher-order structure | nucleosome | linker histone | mesoscale modeling | electron microscopy T he physical packaging of megabase pairs of genomic DNA stored as the chromatin fiber in eukaryotic cell nuclei has been one of the great challenges in biology (1). The limited resolution and disparate levels that can be studied by both experimental and modeling studies of chromatin, which exhibits multiple spatial and temporal scales par excellence, make it challenging to present an integrated structural view, from nucleosomes to chromosomes (2). Because all fundamental template-directed processes of DNA depend on chromatin architecture, advances in our understanding of chromatin higher-order organization are needed to help interpret numerous regulatory events from DNA damage repair to epigenetic control.At the primary structural level, the DNA makes ∼1.7 left-superhelical turns around eight core histones to form a nucleosome core. The nucleosome cores are connected by linker DNA to form nucleosome arrays. An X-ray crystal structure of the nucleosome core has been solved at atomic resolution (3), and a short, four-nucleosome array has also been ...

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Section: Discussionsupporting

confidence: 91%

Section: Mesoscale Modeling Reveals Hierarchically Folded Loops In Chmentioning

confidence: 99%

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Grigoryev

Bascom

Buckwalter

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

126

174

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“…Linker histones have long been thought to be to be involved in compaction of chromatin fibre to a folded 30 nm-thick form (Thoma et al 1979), but the details of how this occurs remain poorly understood. The questions of linker histone to nucleosome stoichiometry (Woodcock et al 2006), and exactly how linker histone binds to chromatin are not settled (Brown et al 2006). …”

Section: Chromatin Fibrementioning

confidence: 99%

Micromechanical studies of mitotic chromosomes

2008

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Mitotic chromosomes respond elastically to forces in the nanonewton range, a property important to transduction of stresses used as mechanical regulatory signals during cell division. In addition to being important biologically, chromosome elasticity can be used as a tool for investigating the folding of chromatin. This paper reviews experiments studying stretching and bending stiffness of mitotic chromosomes, plus experiments where changes in chromosome elasticity resulting from chemical and enzyme treatments were used to analyse connectivity of chromatin inside chromosomes. Experiments with nucleases indicate that non-DNA elements constraining mitotic chromatin must be isolated from one another, leading to the conclusion that mitotic chromosomes have a chromatin Fnetwork_ or Fgel_ organization, with stretches of chromatin strung between Fcrosslinking_ points. The as-yet unresolved questions of the identities of the putative chromatin crosslinkers and their organization inside mitotic chromosomes are discussed.

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“…Histone H1 stabilizes the nucleosome and is important in compaction of chromatin into higher order structures (6,7). Moreover, it has been implicated in transcriptional regulation (8).…”

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confidence: 99%

Translocation of histone H1 subtypes between chromatin and cytoplasm during mitosis in normal human fibroblasts

et al. 2010

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Histone H1 is an important constituent of chromatin, which undergoes major structural rearrangements during mitosis. However, the role of H1, multiple H1 subtypes, and H1 phosphorylation is still unclear. In normal human fibroblasts, phosphorylated H1 was found located in nuclei during prophase and in both cytoplasm and condensed chromosomes during metaphase, anaphase, and telophase as detected by immunocytochemistry. Moreover, we detected remarkable differences in the distribution of the histone H1 subtypes H1.2, H1.3, and H1.5 during mitosis. H1.2 was found in chromatin during prophase and almost solely in the cytoplasm of metaphase and early anaphase cells. In late anaphase, it appeared in both chromatin and cytoplasm and again in chromatin during telophase. H1.5 distribution pattern resembled that of H1.2, but H1.5 was partitioned between chromatin and cytoplasm during metaphase and early anaphase. H1.3 was detected in chromatin in all cell cycle phases. We propose therefore, that H1 subtype translocation during mitosis is controlled by phosphorylation, in combination with H1 subtype inherent affinity. We conclude that H1 subtypes, or their phosphorylated forms, may leave chromatin in a regulated way to give access for chromatin condensing factors or transcriptional regulators during mitosis. ' 2010International Society for Advancement of Cytometry Key terms histone H1; chromatin; cell cycle; mitosis IN the cell cycle, DNA and protein content are duplicated, and the cell divides in two in a strict sequential order of events. During prophase, the replicated chromosomes condense, and the nuclear membrane breaks down in prometaphase. At metaphase, the chromosomes are aligned at the equator of the mitotic spindle, and the sister chromatids are segregated to the two poles of the spindle during anaphase. Finally, the separation is completed during telophase by cytoplasmic division. Impaired cell cycle control or cell cycle progression may result in cell death or malignant transformation.

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Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length

Cited by 414 publications

References 81 publications

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Micromechanical studies of mitotic chromosomes

Translocation of histone H1 subtypes between chromatin and cytoplasm during mitosis in normal human fibroblasts

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