Unique epigenetic influence of H2AX phosphorylation and H3K56 acetylation on normal stem cell radioresponses

Jacobs, Keith M.; Misri, Sandeep; Meyer, Barbara; Raj, Suyash; Zobel, Cheri L.; Sleckman, Barry P.; Hallahan, Dennis E.; Sharma, Girdhar G.

doi:10.1091/mbc.e16-01-0017

Cited by 26 publications

(50 citation statements)

References 59 publications

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“…Figure S2A shows a representative example of an uncropped image of co-plated ESCs and EDCs in same line of microirradiation. Most of the ED cells showed depleted H3K9ac at the DSB track, quantified in the fluorescent signal-intensity line profile across the irradiated nuclei (Figure 2A, upper panel), which does not occur due to eviction of H3 from the damaged sites (Jacobs et al., 2016). But unlike ED, ES cells did not downregulate H3K9ac at the DNA DSBs with same proficiency as observed in ED (Figure 2A, lower panel).…”

Section: Resultsmentioning

confidence: 99%

“…The basal expression of histone H3 was similar between the two cell types (Figure 1A). ES cells in culture were co-plated with isogenic non-stem ED cells before fixation as described previously (Jacobs et al., 2016). H3K9ac was detected with the stem cell-specific transcription factor SOX2.…”

Section: Resultsmentioning

confidence: 99%

“…Immunoblotting also corroborated high H3K9ac in ES compared with ED (Figure 1C). NS cells, isolated from newborn mouse hippocampi compared with their non-stem cell (ND) counterparts, were also investigated (Jacobs et al., 2016). Immunoblotting revealed high H3K9ac in NS compared with SOX2-negative ND (Figure 1D).…”

Section: Resultsmentioning

confidence: 99%

“…These “normal” stem cells are characterized by elevated levels of histone marks associated with active chromatin and lower levels of repressive chromatin (Chen and Dent, 2014). Previously, we have delineated the epigenetic influence of H3K56 acetylation on attenuation of DDR in murine embryonic ES and NS cells, as well as in several tissue niches in vivo, demonstrating H3K56ac as an epigenetic suppressor of DDR that promotes ionizing radiation (IR) hypersensitivity in normal stem cells (Jacobs et al., 2016). …”

Section: Introductionmentioning

confidence: 99%

“…We compared karyotypically normal, early-passage, radiosensitive murine ES and NS with the isogenic radioresistant non-stem cells (ED and ND), proliferating at identical rates in culture; to investigate the differential regulation of DNA damage and apoptotic responses of radiosensitive stem and radioresistant non-stem cells (Jacobs et al., 2016). In this study, we demonstrate constitutively high H3K9ac but low H3K9me3 levels in ES that fails to downregulate H3K9ac at the DSB sites (microirradiation tracks), unlike the ED.…”

Section: Introductionmentioning

confidence: 99%

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Histone H3 Lysine 9 Acetylation Obstructs ATM Activation and Promotes Ionizing Radiation Sensitivity in Normal Stem Cells

et al. 2016

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SummaryDynamic spatiotemporal modification of chromatin around DNA damage is vital for efficient DNA repair. Normal stem cells exhibit an attenuated DNA damage response (DDR), inefficient DNA repair, and high radiosensitivity. The impact of unique chromatin characteristics of stem cells in DDR regulation is not yet recognized. We demonstrate that murine embryonic stem cells (ES) display constitutively elevated acetylation of histone H3 lysine 9 (H3K9ac) and low H3K9 tri-methylation (H3K9me3). DNA damage-induced local deacetylation of H3K9 was abrogated in ES along with the subsequent H3K9me3. Depletion of H3K9ac in ES by suppression of monocytic leukemia zinc finger protein (MOZ) acetyltransferase improved ATM activation, DNA repair, diminished irradiation-induced apoptosis, and enhanced clonogenic survival. Simultaneous suppression of the H3K9 methyltransferase Suv39h1 abrogated the radioprotective effect of MOZ inhibition, suggesting that high H3K9ac promoted by MOZ in ES cells obstructs local upregulation of H3K9me3 and contributes to muted DDR and increased radiosensitivity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Histone H3 Lysine 9 Acetylation Obstructs ATM Activation and Promotes Ionizing Radiation Sensitivity in Normal Stem Cells

et al. 2016

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Epigenetic changes of osteoblasts in response to titanium surface characteristics

Ichioka

Asa’ad

Malekzadeh

et al. 2020

J Biomedical Materials Res

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We aimed to investigate the influence of titanium surface characteristics on epigenetic mechanisms and DNA damage/repair pathways. Osteoblast-like cells (MG63) were incubated on glass, smooth titanium, and minimally rough titanium discs, respectively, for 0, 1, 6, and 24 hr. The presence of double-stranded DNA damage (γH2AX), DNA repair (Chk2), and epigenetic markers (AcH3 & DNMT1) were investigated using immunofluorescence. There were no Chk2-positive cells on the minimally rough titanium surfaces at all-time points, in comparison to glass and smooth titanium. Total γH2AX-positive cells on minimally rough titanium gradually decreased as incubation time increased, on the contrary to smooth titanium. Minimally rough titanium surfaces induced cytoplasmic staining of DNMT1 up to 99% at 24 hr. For epigenetic markers related to the DNA damage/repair pathway, minimally rough titanium surfaces showed the lower percentage of AcH3-positive cells compared to glass and smooth titanium surface. The findings in the current study show that titanium surface characteristics indeed influence DNA damage and the DNA repair pathway, including epigenetic factors.

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When epigenetics meets bioengineering—A material characteristics and surface topography perspective

et al. 2017

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The field of tissue engineering and regenerative medicine (TE/RM) involves regeneration of tissues and organs using implantable biomaterials. The term epigenetics refers to changes in gene expression that are not encoded in the DNA sequence, leading to remodeling of the chromatin and activation or inactivation of gene expression. Recently, studies have demonstrated that these modifications are influenced not only by biological cues but also by mechanical and topographical signals. This review highlights the current knowledge on emerging approaches in TE/RM with a focus on the effect of materials and topography on the epigenetic expression pattern in cells with potential impacts on modulating regenerative biology. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2065-2071, 2018.

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Unique epigenetic influence of H2AX phosphorylation and H3K56 acetylation on normal stem cell radioresponses

Cited by 26 publications

References 59 publications

Histone H3 Lysine 9 Acetylation Obstructs ATM Activation and Promotes Ionizing Radiation Sensitivity in Normal Stem Cells

Histone H3 Lysine 9 Acetylation Obstructs ATM Activation and Promotes Ionizing Radiation Sensitivity in Normal Stem Cells

Epigenetic changes of osteoblasts in response to titanium surface characteristics

When epigenetics meets bioengineering—A material characteristics and surface topography perspective

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