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The histone H4K20 methyltransferase SUV4-20H1/KMT5B is required for multiciliated cell differentiation in Xenopus.
Life Sci. All. 6:16 (2023)
H4 lysine 20 dimethylation (H4K20me2) is the most abundant histone modification in vertebrate chromatin. It arises from sequential methylation of unmodified histone H4 proteins by the mono-methylating enzyme PR-SET7/KMT5A, followed by conversion to the dimethylated state by SUV4-20H (KMT5B/C) enzymes. We have blocked the deposition of this mark by depleting Xenopus embryos of SUV4-20H1/H2 methyltransferases. In the larval epidermis, this results in a severe loss of cilia in multiciliated cells (MCC), a key component of mucociliary epithelia. MCC precursor cells are correctly specified, amplify centrioles, but ultimately fail in ciliogenesis because of the perturbation of cytoplasmic processes. Genome-wide transcriptome profiling reveals that SUV4-20H1/H2-depleted ectodermal explants preferentially down-regulate the expression of several hundred ciliogenic genes. Further analysis demonstrated that knockdown of SUV4-20H1 alone is sufficient to generate the MCC phenotype and that its catalytic activity is needed for axoneme formation. Overexpression of the H4K20me1-specific histone demethylase PHF8/KDM7B also rescues the ciliogenic defect in a significant manner. Taken together, this indicates that the conversion of H4K20me1 to H4K20me2 by SUV4-20H1 is critical for the formation of cilia tufts.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Demethylase Phf8; Genome Integrity; Methylation; Chromatin; Monomethylation; Quiescence; Pr-set7; Cycle
ISSN (print) / ISBN
2575-1077
e-ISSN
2575-1077
Journal
Life Science Alliance
Quellenangaben
Volume: 6,
Issue: 7,
Article Number: 16
Publisher
EMBO Press
Publishing Place
Heidelberg
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)
Grants
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)