2020
DOI: 10.21203/rs.3.rs-51227/v1
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Abstract: Background: Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of H3.3K27M mutation, as well as radiation and bromodomain inhibition (BRDi) with JQ1, on DIPG PTM profiles.Methods: We performed targeted mass spectroscopy on H3.3K27M mutant and wild-type tissues (n=12) and cell lines… Show more

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Cited by 5 publications
(6 citation statements)
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“…Previously, we and others reported that H3K27M DIPG cells exhibit elevated levels of another chromatin-associated histone posttranslational modification, demethylated lysine-36 of histone H3 (H3K36me2) (14)(15)(16). While H3K36me2 is antagonistic to the catalysis of H3K27me2/me3 (17,18), it remains unclear as to whether the elevated levels of H3K36me2 in DIPG arise through the increased levels of transcription in these cells or letup from the antagonistic effects of H3K27me2/me3.…”
Section: Introductionmentioning
confidence: 99%
“…Previously, we and others reported that H3K27M DIPG cells exhibit elevated levels of another chromatin-associated histone posttranslational modification, demethylated lysine-36 of histone H3 (H3K36me2) (14)(15)(16). While H3K36me2 is antagonistic to the catalysis of H3K27me2/me3 (17,18), it remains unclear as to whether the elevated levels of H3K36me2 in DIPG arise through the increased levels of transcription in these cells or letup from the antagonistic effects of H3K27me2/me3.…”
Section: Introductionmentioning
confidence: 99%
“…Recently, H3K36me2 and H4K16Ac were discovered to be novel epigenetic signatures of DIPG (57). H3K4me3, an important histone mark for developmental neurogenesis, was relatively unaffected regardless of these mutations as shown with western blot analysis (14)(15)(16)(17).…”
Section: Discussionmentioning
confidence: 96%
“…These mutations crosstalk with other histone modifications and bring about abnormal gene expression involved in pediatric malignant glioma tumorigenesis. Recently, H3K36me2 and H4K16Ac were discovered to be novel epigenetic signatures of DIPG (57). H3K4me3, an important histone mark for developmental neurogenesis, was relatively unaffected regardless of these mutations as shown with western blot analysis (1417).…”
Section: Discussionmentioning
confidence: 99%
“…Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC), an NAD+-dependent enzyme deeply involved in gene regulation, genome stability maintenance, apoptosis, autophagy, senescence, proliferation, aging, and tumorigenesis (23). Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy (24).SIRT1 regulates macrophage selfrenewal (25) and regulates lipid metabolism, oxidative stress and in ammation in the liver (26).Furthermore,SIRT1 has recently garnered tremendous attention because of its various regulatory effects in several pathological conditions (27).In additional, ATGL promotes autophagy/lipophagy via SIRT1 to control hepatic lipid droplet catabolism(28).H4K16Ac acts as epigenetic signatures of diffuse intrinsic pontine glioma (29).Selective binding of the PHD6 nger of MLL4 to histone H4K16Ac links MLL4 and MOF (30).JMJD6 modulates DNA damage response through downregulating H4K16Ac independently of its enzymatic activity (31).Acetylation of hMOF modulates H4K16Ac to regulate DNA repair genes (32,33). Moreover, our results demonstrate mutant MEG3 enhances the expression of SETD2 dependent on H4K16Ac.…”
Section: Discussionmentioning
confidence: 99%