Possible role of H1 histone in replication timing

Flickinger, R.A.

doi:10.1111/dgd.12190

Cited by 8 publications

(5 citation statements)

References 90 publications

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“…Therefore, it is expected that linker histones have important roles in the control of DNA replication 97 . Surprisingly, early experiments using an in vitro replication system based on viral (simian virus 40 (SV40)) DNA and HeLa cell cytosolic extracts indicated that purified native H1, when present at physiological ratios to nucleosomal histones, failed to repress SV40 replication 98 .…”

Section: Biological Functionsmentioning

confidence: 99%

Emerging roles of linker histones in regulating chromatin structure and function

Fyodorov

Zhou

Skoultchi

et al. 2017

Nat Rev Mol Cell Biol

361

383

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Together with core histones, which make up the nucleosome, the linker histone (H1) is one of the five main histone protein families present in chromatin in eukaryotic cells. H1 binds to the nucleosome to form the next structural unit of metazoan chromatin, the chromatosome, which may help chromatin to fold into higher-order structures. Despite their important roles in regulating the structure and function of chromatin, linker histones have not been studied as extensively as core histones. Nevertheless, substantial progress has been made recently. The first near-atomic resolution crystal structure of a chromatosome core particle and an 11 Å resolution cryo-electron microscopy-derived structure of the 30 nm nucleosome array have been determined, revealing unprecedented details about how linker histones interact with the nucleosome and organize higher-order chromatin structures. Moreover, several new functions of linker histones have been discovered, including their roles in epigenetic regulation and the regulation of DNA replication, DNA repair and genome stability. Studies of the molecular mechanisms of H1 action in these processes suggest a new paradigm for linker histone function beyond its architectural roles in chromatin.

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Section: Biological Functionsmentioning

confidence: 99%

Emerging roles of linker histones in regulating chromatin structure and function

Fyodorov

Zhou

Skoultchi

et al. 2017

Nat Rev Mol Cell Biol

361

383

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“…Such elements either colocalize with replication origins or interact with origins (19,20), creating a chromosomal context permissive for both transcriptional activity and replication initiation (21–23). However, it is unclear how specific histone modifications affect initiation frequency and regulate the rate of DNA synthesis.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylated SIRT1 associates with replication origins to prevent excess replication initiation and preserve genomic stability

Utani

Jang

et al. 2017

Nucleic Acids Research

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Chromatin structure affects DNA replication patterns, but the role of specific chromatin modifiers in regulating the replication process is yet unclear. We report that phosphorylation of the human SIRT1 deacetylase on Threonine 530 (T530-pSIRT1) modulates DNA synthesis. T530-pSIRT1 associates with replication origins and inhibits replication from a group of ‘dormant’ potential replication origins, which initiate replication only when cells are subject to replication stress. Although both active and dormant origins bind T530-pSIRT1, active origins are distinguished from dormant origins by their unique association with an open chromatin mark, histone H3 methylated on lysine 4. SIRT1 phosphorylation also facilitates replication fork elongation. SIRT1 T530 phosphorylation is essential to prevent DNA breakage upon replication stress and cells harboring SIRT1 that cannot be phosphorylated exhibit a high prevalence of extrachromosomal elements, hallmarks of perturbed replication. These observations suggest that SIRT1 phosphorylation modulates the distribution of replication initiation events to insure genomic stability.

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“…2). In addition to playing roles in transcriptional activation,13 histone H1 variants are also linked to DNA replication and repair and mitosis 14–18. While H1 is usually chromatin-bound, the binding is dynamic, further highlighting a direct rather than just reactive role for histone H1 binding in the control of gene expression and genome integrity.…”

Section: Mutations In Histone H1mentioning

confidence: 99%

Histones: coming of age in Mendelian genetic disorders

et al. 2023

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Histones hold significant interest in development and genetic disorders due to their critical roles in chromatin dynamics, influencing gene expression and genome integrity. These roles are linked to alterations of post-translational marks, which are generally concentrated in the histone tails. The machinery modifying or interpreting these marks, known as chromatin writers, erasers or readers, have been associated with many Mendelian disorders; however, it has been only recently that the histone proteins themselves have been directly implicated in Mendelian conditions. High throughput sequencing has recently identified mutations in genes encoding histone H1, H3 and H4, all causing neurodevelopmental disorders with clinical variability. Notably, many of the mutations lie outside of recognised post-translational modification-associated residues, suggesting disrupting the core functions of histones is a primary molecular mechanism underpinning these neurodevelopmental phenotypes. In this review, we describe the clinical and genetic features of histone-related disorders, focusing on the unique aspects associated with each histone gene family, while noting the commonalities which provide insight into the required roles for histone fidelity in brain development and functioning.

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Possible role of H1 histone in replication timing

Cited by 8 publications

References 90 publications

Emerging roles of linker histones in regulating chromatin structure and function

Emerging roles of linker histones in regulating chromatin structure and function

Phosphorylated SIRT1 associates with replication origins to prevent excess replication initiation and preserve genomic stability

Histones: coming of age in Mendelian genetic disorders

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