?

Subcellular localization

Ciliary associated gene, Nucleoplasm, Cytosol

Functional category

• Motors (dynein/kinesin)

Function

Congenital heart disease affects 1% of infants, and variants were identified affecting genes (RNF20, RNF40, and UBE2B) involved in a chromatin modification called histone 2B monoubiquitination (H2Bub1). How these variants lead to congenital heart disease remains unknown. Here, we demonstrate how H2Bub1 pathway modulation during development leads to abnormal cardiac left–right patterning. In Xenopus, H2Bub1 regulates cilia motility, and defects lead to abnormal inner dynein arms, mirroring a patient with an RNF20 mutation. Moreover, we show that H2Bub1 marks are enriched on the cilia transcription factor Rfx3 in a tissue-specific manner, furthermore, addition of rfx3 mRNA to Rnf20-depleted embryos restores cilia motility. Thus, our findings uncover a mechanism linking H2Bub1 with cilia and cardiac development(31235600).