RT @HironoriFunabi1: Here is the link to a news letter article covering our finding.

RT @HironoriFunabi1: Excited to share the revised version with a new title "CDCA7 is an evolutionarily conserved hemimethylated DNA sensor….

RT @ArmrYshr: Please repost!.Arimura Lab is hiring! We are seeking the next generation of MagICians (technicians and a postdoc) to elucidat….

RT @ArmrYshr: Excited to share my final PostDoc work! Introducing MagIC-cryo-EM🪄 & DuSTER🧹, these methods reduce cryo-EM sample requirement….

We’re excited to investigate the ways in which the recognition of hemi-methylated CpG by CDCA7 may differ from its recognition by UHRF1. Currently having fun thinking about the potential roles of a hemi-methylation sensor… better get back to the bench! @HironoriFunabi1 7/7.

…saw the specific accumulation of CDCA7 on hemi-methylated DNA, which also recruits HELLS. Suddenly, the unique role of the CDCA7-HELLS nucleosome remodeler in DNA methylation starts to make more sense. As always, several intriguing questions remain. 6/7

This got us thinking about DNA methylation maintenance, where hemi-methylated DNA is targeted by UHRF1 and DNMT1 to re-establish symmetric CpG methylation behind the replication fork. We made some hemi-methylated DNA, went fishing in Xenopus egg extract and… 5/7.

Our previous coevolutionary analysis suggests the linkage of CDCA7 and HELLS with proteins essential to DNA methylation maintenance: DNMT1 and UHRF1. CDCA7 and HELLS may be uniquely specialized to deal with DNA methylation throughout eukaryote evolution (Funabiki et al. 2023) 4/7

It was proposed that CDCA7-HELLS nucleosome remodeling facilitates DNA accessibility to DNA methyltransferases. But several SNF2 family ATPases exhibit similar nucleosome sliding activities and are not implicated in DNA methylation. What’s so special about CDCA7-HELLS? 3/7.

Back in 2017, the lab identified CDCA7 as the critical activator of the SNF2 family ATPase HELLS: without CDCA7, HELLS cannot remodel nucleosomes (Jenness et al. 2017). Mutations in CDCA7 or HELLS give rise to ICF syndrome, a disorder associated with DNA hypomethylation. 2/7.

Very excited to announce our pre-print! Together with the labs of @NishiyamaAtsuya and @KyoheiArita, we’ve discovered that the protein CDCA7 (a long-time favourite in the Funabiki lab) exhibits a striking ability to sense hemi-methylated DNA. 1/7.