H19/Igf2 Expression and Methylation of Histone 3 in Mice Chimeric Blastocysts

Mixed Lineage Leukemia 1 (MLL1), an important member of Histone Methyltransferases (HMT) family, is capable of catalyzing mono-, di-, and trimethylation of Histone 3 lysine 4 (H3K4). The optimal catalytic activity of MLL1 requires the formation of a core complex consisting of MLL1, WDR5, RbBP5, and ASH2L. The Protein-Protein Interaction (PPI) between WDR5 and MLL1 plays an important role in abnormal gene expression during tumorigenesis, and disturbing this interaction may have a potential for the treatment of leukemia harboring MLL1 fusion proteins. In this review, we will summarize recent progress in the development of inhibitors targeting MLL1- WDR5 interaction.

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Isolation and characterization of TH3, a germ cell-specific variant of histone 3 in rat testis.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)47220-6 ◽

1984 ◽

Vol 259 (14) ◽

pp. 8769-8776

Author(s):

P K Trostle-Weige ◽

M L Meistrich ◽

W A Brock ◽

K Nishioka

Keyword(s):

Germ Cell ◽

Rat Testis ◽

Histone 3 ◽

Isolation And Characterization

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A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation

Molecular Cell ◽

10.1016/j.molcel.2021.01.041 ◽

2021 ◽

Author(s):

Isabel Regadas ◽

Olle Dahlberg ◽

Roshan Vaid ◽

Oanh Ho ◽

Sergey Belikov ◽

...

Keyword(s):

Gene Regulation ◽

Specific Gene ◽

Chromatin Signature ◽

Tissue Specific ◽

Tissue Specific Gene ◽

Histone 3

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Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

International Journal of Molecular Sciences ◽

10.3390/ijms22157813 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7813

Author(s):

Lindsay Kraus ◽

Chris Bryan ◽

Marcus Wagner ◽

Tabito Kino ◽

Melissa Gunchenko ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Dna Damage ◽

Stem Cell ◽

Histone Modification ◽

Epigenetic Regulation ◽

Critical Role ◽

Proliferative Potential ◽

Therapeutic Effects ◽

Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

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PATH-17. NOVEL DUAL HISTONE 3 K27M AND G34R POINT MUTATIONS IN A MIDLINE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.699 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii167-ii167

Author(s):

Peter Pan ◽

Tejus Bale ◽

Alexandra Miller ◽

Marc Ladanyi ◽

Marc Rosenblum ◽

...

Keyword(s):

Point Mutations ◽

Histone 3 ◽

First Case ◽

Microvascular Proliferation ◽

Motor Neuron Facial Nerve ◽

Methylguanine Methyltransferase ◽

Mitotic Figures ◽

In Cis ◽

Generation Sequencing ◽

Diffuse Midline Glioma

Abstract BACKGROUND Histone H3 alterations due to mutations on H3F3A and HIST1H3B genes, have in recent years been associated with distinct entities and tumor locations within the context of infiltrative gliomas. H3K27M is associated with a midline location and is included in the WHO 2016 as the diffuse midline glioma H3K27M-mutant, a specific diagnostic entity. H3G34R, thought to be a mutually exclusive alteration, is less common but has been associated with a cerebral hemispheric location. We report the first case to our knowledge with both of these alterations in the same tumor. METHODS Clinical and pathologic records of the patient were reviewed and presented. RESULTS A 39-year-old man presented with acute right face, arm, and leg numbness and mild weakness; examination was notable for right lower motor neuron facial nerve palsy and numbness, along with numbness and subtle slowing of rapid alternating movements in the left arm and leg. A non-enhancing left thalamic mass was identified and stereotactically biopsied. Infiltrative glial neoplasm with moderately-increased cellularity was seen, with ovoid cells, enlarged nuclei, apoptotic bodies, and mitotic figures. No necrosis or microvascular proliferation seen. Immunostain was positive for H3K27M. O6-methylguanine-methyltransferase (MGMT) promoter was not methylated. Next-generation sequencing showed dual in cis H3 point mutations in K27M (HIST1H3B c.83A >T) and G34R (HIST1H3B c.103G >C). Additional alterations were noted in NF1, PIK3CA, ATRX, FGFR3, and NSD1. Isocitrate dehydrogenase (IDH1/2) mutations were not identified. CONCLUSION This case of a young man with a midline glioma is novel for carrying both H3K27M and H3G34R alterations and indicates these alterations are not mutually exclusive. The interaction seen here suggests H3K27M dominance for a midline phenotype.

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Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3

Nature Communications ◽

10.1038/s41467-021-23510-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Laura Santini ◽

Florian Halbritter ◽

Fabian Titz-Teixeira ◽

Toru Suzuki ◽

Maki Asami ◽

...

Keyword(s):

Bisulfite Sequencing ◽

Blastocyst Stage ◽

Preimplantation Embryos ◽

Imprinted Genes ◽

Specific Expression ◽

Histone 3 ◽

Complex Program ◽

Genome Bisulfite Sequencing ◽

Mammalian Genomes ◽

Parent Of Origin

AbstractIn mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.

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Cyclophilin BcCyp2 Regulates Infection-Related Development to Facilitate Virulence of the Gray Mold Fungus Botrytis cinerea

International Journal of Molecular Sciences ◽

10.3390/ijms22041694 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1694

Author(s):

Jiao Sun ◽

Chen-Hao Sun ◽

Hao-Wu Chang ◽

Song Yang ◽

Yue Liu ◽

...

Keyword(s):

Botrytis Cinerea ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Gray Mold ◽

Gene Encoding ◽

Histone 3 ◽

Mold Fungus ◽

Related Development ◽

Hyphal Morphology ◽

Cellular Components

Cyclophilin (Cyp) and Ca2+/calcineurin proteins are cellular components related to fungal morphogenesis and virulence; however, their roles in mediating the pathogenesis of Botrytis cinerea, the causative agent of gray mold on over 1000 plant species, remain largely unexplored. Here, we show that disruption of cyclophilin gene BcCYP2 did not impair the pathogen mycelial growth, osmotic and oxidative stress adaptation as well as cell wall integrity, but delayed conidial germination and germling development, altered conidial and sclerotial morphology, reduced infection cushion (IC) formation, sclerotial production and virulence. Exogenous cyclic adenosine monophosphate (cAMP) rescued the deficiency of IC formation of the ∆Bccyp2 mutants, and exogenous cyclosporine A (CsA), an inhibitor targeting cyclophilins, altered hyphal morphology and prevented host-cell penetration in the BcCYP2 harboring strains. Moreover, calcineurin-dependent (CND) genes are differentially expressed in strains losing BcCYP2 in the presence of CsA, suggesting that BcCyp2 functions in the upstream of cAMP- and Ca2+/calcineurin-dependent signaling pathways. Interestingly, during IC formation, expression of BcCYP2 is downregulated in a mutant losing BcJAR1, a gene encoding histone 3 lysine 4 (H3K4) demethylase that regulates fungal development and pathogenesis, in B. cinerea, implying that BcCyp2 functions under the control of BcJar1. Collectively, our findings provide new insights into cyclophilins mediating the pathogenesis of B. cinerea and potential targets for drug intervention for fungal diseases.

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