Histone modifications and the DNA double-strand break response

Van, Hieu T.; Santos, Margarida A.

doi:10.1080/15384101.2018.1542899

Cited by 57 publications

(39 citation statements)

References 78 publications

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“…These different epigenetic mechanisms can function coordinately via interactions and cross-talk to form layers of regulation [25,26,27■,28]. The histones around which DNA is wrapped are subject to a series of modifications including acetylation, methylation, ubiquitination and phosphorylation [29]. These histone modifications are usually located on the histone tails and can directly affect chromatin structure, which further defines active or repressed gene expression states.…”

Section: Epigenetic Regulation Of Hsc Homingmentioning

confidence: 99%

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation

Huang

Broxmeyer

2019

Current Opinion in Hematology

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Hematopoietic cell transplantation (HCT) is a life-saving treatment for a variety of hematological and non-hematological disorders. Successful clinical outcomes after transplantation rely on adequate hematopoietic stem cell (HSC) numbers, and the homing and subsequent short-and long-term engraftment of these cells in the bone marrow. Enhancing the homing capability of HSCs has the potential for high impact on improving HCT and patient survival. Recent findings There are a number of ways to enhance HSC engraftment. Neutralizing negative epigenetic regulation by histone deacetylase 5 (HDAC5) increases surface CXCR4 expression and promotes human HSC homing and engraftment in immune deficient (NSG) mice. Short-term treatment of cells with glucocorticoids, pharmacological stabilization of hypoxia inducible factor (HIF)-1α, increasing membrane lipid raft aggregation, and inhibition of Dipeptidyl peptidase 4 (DPP4) facilitates HSC homing and engraftment. Added to these procedures, modulating the mitochondria permeability transition pore (MPTP) to mitigate ambient air induced Extra Physiological Oxygen Stress/Shock (EPHOSS) by hypoxic harvest and processing, or using cyclosporine A during air collection increases functional HSC numbers and improves HSC engraftment. Summary A Better understanding of the regulation of human HSC homing mediated by various signaling pathways will facilitate development of more efficient means to enhance HCT efficacy.

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Section: Epigenetic Regulation Of Hsc Homingmentioning

confidence: 99%

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation

Huang

Broxmeyer

2019

Current Opinion in Hematology

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“…There is evidence from studies in somatic cells that changes in epigenetic marks modulate genome damage responses (GDR). Indeed, chromatin needs to be quickly remodeled at the sites of DNA double-strand breaks (DSBs) to allow specific repair factors access to act and repair the damaged DNA sites (Ayrapetov et al, 2014;Van and Santos, 2018;Nakamura et al, 2019;Sharma and Hendzel, 2019). Histone lysine demethylases of H3K4, including KDM1A, KDM5A, and KDM5B (Faucher and Wellinger, 2010;Li et al, 2014;Gong et al, 2017), as well as KDMs of H3K9, including KDM4B andKDM4D (Khoury-Haddad et al, 2014, 2015), were shown to be involved in the GDR process.…”

Section: Introductionmentioning

confidence: 99%

Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos

Glanzner

Gutierrez

Rissi

et al. 2020

Front. Cell Dev. Biol.

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The lysine demethylases KDM5B and KDM5C are highly, but transiently, expressed in porcine embryos around the genome activation stage. Attenuation of KDM5B and KDM5C mRNA hampered embryo development to the blastocyst stage in fertilized, parthenogenetically activated and nuclear transfer embryos. While KDM5B attenuation increased H3K4me2-3 levels on D3 embryos and H3K4me1-2-3 on D5 embryos, KDM5C attenuation increased H3K9me1 on D3 embryos, and H3K9me1 and H3K4me1 on D5 embryos. The relative mRNA abundance of EIF1AX and EIF2A on D3 embryos, and the proportion of D4 embryos presenting a fluorescent signal for uridine incorporation were severely reduced in both KDM5B-and KDM5Cattenuated compared to control embryos, which indicate a delay in the initiation of the embryo transcriptional activity. Moreover, KDM5B and KDM5C attenuation affected DNA damage response and increased DNA double-strand breaks (DSBs), and decreased development of UV-irradiated embryos. Findings from this study revealed that both KDM5B and KDM5C are important regulators of early development in porcine embryos as their attenuation altered H3K4 and H3K9 methylation patterns, perturbed embryo genome activation, and decreased DNA damage repair capacity.

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“…Histone proteins are subjected to a wide variety of posttranslational modifications, known as histone marks, that decorate distinct chromatin regions (3). Modification of chromatin structure controls a plethora of nuclear processes, including gene expression and DNA repair and replication (3, 4). Consequently, genome-wide maps of histone modifications have been instrumental in identifying functionally different regions of eukaryotic genomes (5, 6).…”

Section: Introductionmentioning

confidence: 99%

Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen Candida albicans

Price

Weindling

Berman

et al. 2019

mBio

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Eukaryotic genomes are packaged into chromatin structures that play pivotal roles in regulating all DNA-associated processes. Histone posttranslational modifications modulate chromatin structure and function, leading to rapid regulation of gene expression and genome stability, key steps in environmental adaptation. Candida albicans, a prevalent fungal pathogen in humans, can rapidly adapt and thrive in diverse host niches. The contribution of chromatin to C. albicans biology is largely unexplored. Here, we generated the first comprehensive chromatin profile of histone modifications (histone H3 trimethylated on lysine 4 [H3K4me3], histone H3 acetylated on lysine 9 [H3K9Ac], acetylated lysine 16 on histone H4 [H4K16Ac], and γH2A) across the C. albicans genome and investigated its relationship to gene expression by harnessing genome-wide sequencing approaches. We demonstrated that gene-rich nonrepetitive regions are packaged into canonical euchromatin in association with histone modifications that mirror their transcriptional activity. In contrast, repetitive regions are assembled into distinct chromatin states; subtelomeric regions and the ribosomal DNA (rDNA) locus are assembled into heterochromatin, while major repeat sequences and transposons are packaged in chromatin that bears features of euchromatin and heterochromatin. Genome-wide mapping of γH2A, a marker of genome instability, identified potential recombination-prone genomic loci. Finally, we present the first quantitative chromatin profiling in C. albicans to delineate the role of the chromatin modifiers Sir2 and Set1 in controlling chromatin structure and gene expression. This report presents the first genome-wide chromatin profiling of histone modifications associated with the C. albicans genome. These epigenomic maps provide an invaluable resource to understand the contribution of chromatin to C. albicans biology and identify aspects of C. albicans chromatin organization that differ from that of other yeasts. IMPORTANCE The fungus Candida albicans is an opportunistic pathogen that normally lives on the human body without causing any harm. However, C. albicans is also a dangerous pathogen responsible for millions of infections annually. C. albicans is such a successful pathogen because it can adapt to and thrive in different environments. Chemical modifications of chromatin, the structure that packages DNA into cells, can allow environmental adaptation by regulating gene expression and genome organization. Surprisingly, the contribution of chromatin modification to C. albicans biology is still largely unknown. For the first time, we analyzed C. albicans chromatin modifications on a genome-wide basis. We demonstrate that specific chromatin states are associated with distinct regions of the C. albicans genome and identify the roles of the chromatin modifiers Sir2 and Set1 in shaping C. albicans chromatin and gene expression.

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Histone modifications and the DNA double-strand break response

Cited by 57 publications

References 78 publications

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation

Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos

Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen Candida albicans

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