Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation

Lercher, Lukas; Raj, Ritu; Patel, Nisha; Price, Joshua; Mohammed, Shabaz; Robinson, Carol V.; Schofield, Christopher J.; Davis, Benjamin G.

doi:10.1038/ncomms8978

Cited by 54 publications

(57 citation statements)

References 52 publications

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“…Potentially, O-GlcNAcylation could influence the loading of newly replicated DNA on the histone and histone assembly or disassembly. For example, reconstituted synthetic histone nucleosomes show destabilized H2A–H2B dimers, which mimic an open chromatin state [35]. Furthermore, the histone chaperone complex FACT (Facilitates chromatin transcripts) interacts with synthetic nucleosomes containing a synthetic O -GlcNAc site at H2A-S112 [36], while OGT is known to interact with the histone chaperone HIRA complex promoting nucleosome assembly of H3.3 [37].…”

Section: O-glcnac Cycling In Interphasementioning

confidence: 99%

The sweet side of the cell cycle

Tan

Duncan

Slawson

2017

Biochemical Society Transactions

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Cell division (mitosis) and gamete production (meiosis) are fundamental requirements for normal organismal development. The mammalian cell cycle is tightly regulated by different checkpoints ensuring complete and precise chromosomal segregation and duplication. In recent years, researchers have become increasingly interested in understanding how O-GlcNAc regulates the cell cycle. The O-GlcNAc post-translation modification is an O-glycosidic bond of a single β-N-acetylglucosamine sugar to serine/threonine residues of intracellular proteins. This modification is sensitive toward changes in nutrient levels in the cellular environment making O-GlcNAc a nutrient sensor capable of influencing cell growth and proliferation. Numerous studies have established that O-GlcNAcylation is essential in regulating mitosis and meiosis, while loss of O-GlcNAcylation is lethal in growing cells. Moreover, aberrant O-GlcNAcylation is linked with cancer and chromosomal segregation errors. In this review, we will discuss how O-GlcNAc controls different aspects of the cell cycle with a particular emphasis on mitosis and meiosis.

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Section: O-glcnac Cycling In Interphasementioning

confidence: 99%

The sweet side of the cell cycle

Tan

Duncan

Slawson

2017

Biochemical Society Transactions

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“…The CD spectra for both the reconstituted nucleosomes were essentially identical and the melting temperatures measured by variabletemperature CD analysis were similar (at 220 nm: T m wt= 73.25+/−0.61 °C, T m GlcNAcylated=74.63+/−1.16 °C; at 260 nm: T m wt=71.86+/−0.25 °C, T m GlcNAcylated=70.63+/−0.36 °C) suggesting that GlcNAcylation at the site does not affect the stability of the nucleosome (Figure S10–S14). These combined data suggest that the differential stability mechanism observed for H2A‐T101 GlcNAcylation6 does not operate in H2B‐S112 GlcNAcylation.…”

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confidence: 85%

Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex

et al. 2016

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Transcriptional regulation can be established by various post‐translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. Functional consequences of histone O‐GlcNAcylation (O‐GlcNAc=O‐linked β‐N‐acetylglucosamine) are largely unexplored. Herein, we generate homogeneously GlcNAcylated histones and nucleosomes by chemical post‐translational modification. Mass‐spectrometry‐based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the “facilitates chromatin transcription” (FACT) complex. Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O‐GlcNAcylation as one of the triggers for FACT‐driven transcriptional control.

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“…Davis and co‐workers developed a selective labeling reaction, in which cysteine was converted to dehydroalanine and led to the subsequent installation of several PTMs, including phosphorylation and glycosylation . They applied the reaction to proteomic analysis, utilizing the nucleosome containing GlcNAcylation‐labeled histones ,…”

Section: Chemical Protein Synthesis That Advances Research On Histonementioning

confidence: 99%

Chemistry‐Driven Epigenetic Investigation of Histone and DNA Modifications

Sueoka

Koyama

Hayashi

et al. 2018

The Chemical Record

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In the regulation processes of gene expression, genomic DNA and nuclear proteins, including histone proteins, cooperate with each other, leading to the distinctive functions of eukaryotic cells such as pluripotency and differentiation. Chemical modification of histone proteins and DNA has been revealed as one of the major driving forces in the complicated epigenetic regulation system. However, understanding of the precise molecular mechanisms is still limited. To address this issue, researchers have proposed both biological and chemical strategies for the preparation and detection of modified proteins and nucleic acids. In this review, we focus on chemical methods around the field of epigenetics. Chemical protein synthesis has enabled the preparation of site-specifically modified histones and their successful application to various in vitro assays, which have emphasized the significance of posttranslational modifications of interest. We also review the modification-specific chemical reactions against synthetic and genomic DNA, which enabled discrimination of several modified bases at single-base resolution.

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Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation

Cited by 54 publications

References 52 publications

The sweet side of the cell cycle

The sweet side of the cell cycle

Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex

Chemistry‐Driven Epigenetic Investigation of Histone and DNA Modifications

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