PT  - JOURNAL ARTICLE
AU  - Angerilli, Alessandro
AU  - Tait, Janet
AU  - Berges, Julian
AU  - Shcherbakova, Irina
AU  - Pokrovsky, Daniil
AU  - Schauer, Tamas
AU  - Smialowski, Pawel
AU  - Hsam, Ohnmar
AU  - Mentele, Edith
AU  - Nicetto, Dario
AU  - Rupp, Ralph AW
TI  - The histone H4K20 methyltransferase SUV4-20H1/KMT5B is required for multiciliated cell differentiation in Xenopus
AID  - 10.26508/lsa.202302023
DP  - 2023 Jul 01
TA  - Life Science Alliance
PG  - e202302023
VI  - 6
IP  - 7
4099  - https://www.life-science-alliance.org/content/6/7/e202302023.short
4100  - https://www.life-science-alliance.org/content/6/7/e202302023.full
SO  - Life Sci. Alliance2023 Jul 01; 6
AB  - 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.