Linker histones and chromatin remodelling complexes maintain genome stability and control cellular ageing

Miloshev, George; Staneva, Dessislava; Uzunova, Katya; Vasileva, Bela; Draganova-Filipova, Milena; Zagorchev, Plamen; Georgieva, Milena

doi:10.1016/j.mad.2018.07.002

Cited by 9 publications

(28 citation statements)

References 58 publications

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“…The hho1delta mutant has a deleted gene for the linker histone, HHO1 [ 34 ], the arp4 mutant has a point mutation in the gene for Arp4p [ 34 ], while the double mutant arp4 hho1delta , combines the two mutations [ 35 ]. The strains were selected from our previous work [ 33 ] to allow monitoring of the chronological lifespan in different chromatin backgrounds under UVA-B stress and our previous results have shown that the three chromatin mutants have defects in their chromatin loop organization [ 26 , 35 ] and impaired, accelerated chronological aging. Moreover, to further discuss the interaction between the yeast linker histone Hho1p and Arp4p we have to point to the fact that ACT3/ARP4 is an essential gene, coding for the actin-related protein Act3p/Arp4 of Saccharomyces cerevisiae located within the nucleus.…”

Section: Resultsmentioning

confidence: 99%

“…These data were prerequisite for all following yeast CLS experiments as they gave the foundations of the whole work afterward. Our previous studies with the CLS of the four strains published in [ 26 ] have investigated the survival and aging of the same yeast cell cultures for a period of 19 days. These results have demonstrated that at day 9 we already had prematurely aged cells among the double mutant, while the hho1delta mutants exhibited better survival under optimal CLS conditions than all other strains.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we deliberately chose to monitor the CLS of the four strains in the current study until day 9. This allowed us to study the CLS under UVA/B stress conditions without losing most of the cells in the double mutant as already prematurely dead as shown in [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

“…This gives another evidence for a link between aging and disrupted chromatin structure [ 23 , 24 ]. As essential counterparts of the higher-order chromatin organization, the linker histones are important players in aging and stress adaptation [ 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Vasileva

Staneva

Krasteva

et al. 2021

Cells

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Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes exist and they are evolutionarily conserved among eukaryotes. The linker histones are the fifth class and over time, their role in chromatin has been neglected. Linker histones interact with DNA and the other histones and thus sustain genome stability and nuclear organization. Saccharomyces cerevisiae is a brilliant model for studying linker histones as the gene for it is a single-copy and is non-essential. We, therefore, created a linker histone-free yeast strain using a knockout of the relevant gene and traced the way cells age chronologically. Here we present our results demonstrating that the altered chromatin dynamics during the chronological lifespan of the yeast cells with a mutation in ARP4 (the actin-related protein 4) and without the gene HHO1 for the linker histone leads to strong alterations in the gene expression profiles of a subset of genes involved in DNA repair and autophagy. The obtained results further prove that the yeast mutants have reduced survival upon UVA/B irradiation possibly due to the accelerated decompaction of chromatin and impaired proliferation. Our hypothesis posits that the higher-order chromatin structure and the interactions among chromatin proteins are crucial for the maintenance of chromatin organization during chronological aging under optimal and UVA-B stress conditions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Vasileva

Staneva

Krasteva

et al. 2021

Cells

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“…For example, chromosome territories are the dynamic three-dimensional volumes occupied by each chromosome within the nucleus [27,28]. These non-static volumes are subject to spatial shifting in response to mitotic signaling [29,30], cellular aging cues [31], and DNA damage [32,33]. Chromosome territory dynamics facilitate gene positioning for transcriptional control [34], as well as gene triage for DNA repair [35].…”

Section: Chromatin Organization and Dynamicsmentioning

confidence: 99%

Nuclear Envelope Regulation of Oncogenic Processes: Roles in Pancreatic Cancer

Preston

Faustino

2018

Epigenomes

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Pancreatic cancer is an aggressive and intractable malignancy with high mortality. This is due in part to a high resistance to chemotherapeutics and radiation treatment conferred by diverse regulatory mechanisms. Among these, constituents of the nuclear envelope play a significant role in regulating oncogenesis and pancreatic tumor biology, and this review focuses on three specific components and their roles in cancer. The LINC complex is a nuclear envelope component formed by proteins with SUN and KASH domains that interact in the periplasmic space of the nuclear envelope. These interactions functionally and structurally couple the cytoskeleton to chromatin and facilitates gene regulation informed by cytoplasmic activity. Furthermore, cancer cell invasiveness is impacted by LINC complex biology. The nuclear lamina is adjacent to the inner nuclear membrane of the nuclear envelope and can actively regulate chromatin in addition to providing structural integrity to the nucleus. A disrupted lamina can impart biophysical compromise to nuclear structure and function, as well as form dysfunctional micronuclei that may lead to genomic instability and chromothripsis. In close relationship to the nuclear lamina is the nuclear pore complex, a large megadalton structure that spans both outer and inner membranes of the nuclear envelope. The nuclear pore complex mediates bidirectional nucleocytoplasmic transport and is comprised of specialized proteins called nucleoporins that are overexpressed in many cancers and are diagnostic markers for oncogenesis. Furthermore, recent demonstration of gene regulatory functions for discrete nucleoporins independent of their nuclear trafficking function suggests that these proteins may contribute more to malignant phenotypes beyond serving as biomarkers. The nuclear envelope is thus a complex, intricate regulator of cell signaling, with roles in pancreatic tumorigenesis and general oncogenic transformation.

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The linker histone Hho1 modulates the activity of ATP-dependent chromatin remodeling complexes

Amigo

Farkas

Gidi

et al. 2022

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Linker histones and chromatin remodelling complexes maintain genome stability and control cellular ageing

Cited by 9 publications

References 58 publications

Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Nuclear Envelope Regulation of Oncogenic Processes: Roles in Pancreatic Cancer

The linker histone Hho1 modulates the activity of ATP-dependent chromatin remodeling complexes

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