Histone Variants: Guardians of Genome Integrity

J, Ferrand; Rondinelli, Beatrice; Polo, Sophie E.

doi:10.3390/cells9112424

Cited by 27 publications

(11 citation statements)

References 257 publications

(356 reference statements)

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“…Contrastingly, no such an asymmetry of either H4 (Movie S4) or H2A (Movie S6) was detected in SGs (Figure 1C). The differences among H2A, H3, and H4 likely reflect that both H2A and H3 have variants, such as H3.3 and H2A.v (Ferrand et al, 2020; Henikoff and Smith, 2015; Szenker et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

Differential condensation of sister chromatids coordinates with Cdc6 to ensure distinct cell cycle progression inDrosophilamale germline stem cell lineage

Ranjan

Snedeker

Wooten

et al. 2021

Preprint

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Stem cells undergo asymmetric division to produce both a self-renewing stem cell and a differentiating daughter cell. During Drosophila male germline stem cell (GSC) asymmetric division, preexisting old histones H3 and H4 are enriched in the self-renewed stem daughter cell, whereas the newly synthesized H3 and H4 are enriched in the differentiating daughter cell. However, the biological consequences in the two daughter cells resulting from asymmetric histone inheritance remained to be elucidated. In this work, we track both old and new histones throughout GSC cell cycle using high spatial and temporal resolution microscopy. We find several unique features differentiating old versus new histone-enriched sister chromatids, including nucleosome density, chromosomal condensation, and H3 Ser10 phosphorylation. These distinct chromosomal features lead to their differential association with Cdc6, an essential component of the pre-replication complex, which subsequently contributes to asynchronous initiation of DNA replication in the two resulting daughter cells. Disruption of asymmetric histone inheritance abolishes both differential Cdc6 association and asynchronous S-phase entry, demonstrating that asymmetric histone acts upstream of these critical events during cell cycle progression. Furthermore, GSC defects are detected under these conditions, indicating a connection between histone inheritance, cell cycle progression and cell fate decision. Together, these studies reveal that cell cycle remodeling as a crucial biological readout of asymmetric histone inheritance, which precedes and could lead to other well-known readouts such as differential gene expression. This work also enhances our understanding of asymmetric histone inheritance and epigenetic regulation in other stem cells or asymmetrically dividing cells in multicellular organisms.

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Section: Resultsmentioning

confidence: 99%

Differential condensation of sister chromatids coordinates with Cdc6 to ensure distinct cell cycle progression inDrosophilamale germline stem cell lineage

Ranjan

Snedeker

Wooten

et al. 2021

Preprint

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“…Less is known about how the normal state of chromatin is restored after repair and how defects in this process affect genome integrity. However, the critical role of histone chaperones in restoring chromatin architecture after damage is beginning to be unveiled [ 50 ]. The following sections describe how chromatin mobility is also a key determinant during damage and during chromatin repair to restore genome integrity.…”

Section: The 3rs Of Double-strand Breaks; Response Repair and Restora...mentioning

confidence: 99%

The Dynamic Behavior of Chromatin in Response to DNA Double-Strand Breaks

Fernández

Fabre

2022

Genes

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The primary functions of the eukaryotic nucleus as a site for the storage, retrieval, and replication of information require a highly dynamic chromatin organization, which can be affected by the presence of DNA damage. In response to double-strand breaks (DSBs), the mobility of chromatin at the break site is severely affected and, to a lesser extent, that of other chromosomes. The how and why of such movement has been widely studied over the last two decades, leading to different mechanistic models and proposed potential roles underlying both local and global mobility. Here, we review the state of the knowledge on current issues affecting chromatin mobility upon DSBs, and highlight its role as a crucial step in the DNA damage response (DDR).

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“…Epigenetic regulation has been extensively reviewed in association with various human biological processes, such as embryogenesis, cell differentiation, X chromosome inactivation, and pathologies such as cancer [ 40 , 41 ]. The best-characterized epigenetic mechanisms are DNA methylation and histone modifications; however, the epigenetic scenario is much more complicated with new players and new mechanisms including non-coding RNA (ncRNA)-mediated regulation, histone variants, and ATP-dependent chromatin remodeling [ 42 , 43 , 44 ]. All these discrete but reversible modifications may orchestrate extensive changes in chromatin structure and conformation, interfering with the transcriptional machinery’s ability to access its target genes and promoters [ 45 , 46 ].…”

Section: Epigenetics: Another Layer Of Information In Gene Expression Regulationmentioning

confidence: 99%

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Dobre

Constantin

Costache

et al. 2021

JPM

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Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.

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Histone Variants: Guardians of Genome Integrity

Cited by 27 publications

References 257 publications

Differential condensation of sister chromatids coordinates with Cdc6 to ensure distinct cell cycle progression inDrosophilamale germline stem cell lineage

Differential condensation of sister chromatids coordinates with Cdc6 to ensure distinct cell cycle progression inDrosophilamale germline stem cell lineage

The Dynamic Behavior of Chromatin in Response to DNA Double-Strand Breaks

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

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