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XB-ART-59747
Life Sci Alliance 2023 Jul 01;67:. doi: 10.26508/lsa.202302023.
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The histone H4K20 methyltransferase SUV4-20H1/KMT5B is required for multiciliated cell differentiation in Xenopus.

Angerilli A , Tait J , Berges J , Shcherbakova I , Pokrovsky D , Schauer T , Smialowski P , Hsam O , Mentele E , Nicetto D , Rupp RA .


Abstract
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.

PubMed ID: 37116939
PMC ID: PMC10147948
Article link: Life Sci Alliance


Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: acss2.1 foxj1 hyls1 kmt5a kmt5b kmt5c mcc phf8 tuba4b
GO keywords: cytoskeleton [+]
Antibodies: Tuba4b Ab5
Morpholinos: kmt5b MO1 kmt5c MO1 kmt5c MO2

Disease Ontology terms: Meckel syndrome [+]
GEO Series: GSE161247: NCBI
GSE161248: NCBI
GSE161249: NCBI
GSE161250: NCBI
Phenotypes: Xla Wt + kmt5c MO (suv4-20h2) (Fig.1A') [+]

Article Images: [+] show captions
References [+] :
Al Jord, Calibrated mitotic oscillator drives motile ciliogenesis. 2017, Pubmed