Jūmonji (十文字) isn’t the same as Jumanji. PubMed now prompts people who search there for Jumanji, “𝐷𝑖𝑑 𝑦𝑜𝑢 𝑚𝑒𝑎𝑛 𝐽𝑢𝑚𝑜𝑛𝑗𝑖?” A brief educational thread at the intersection of biology and pop culture… /1
First, biology. In 1995 a group led by Takashi Takeuchi (pictured) & Toru Higashinakagawa at Mitsubishi Kasei Institute of Life Sciences in Tokyo (founded 1971, dissolved 2010) were studying development in mice using a gene trap assay, and noticed a peculiar neural tube defect./2
In their @GenesDev paper, they wrote, “We named this mutation 'jumonji' because the morphology produced by the normal neural groove and abnormal grooves resembles a cross (jumonji is translated as cruciform in Japanese).” Here you can see the cross-shaped embryonal pattern./3
They called the novel protein responsible for this cruciform defect “jmj.” It's encoded in humans by 𝘑𝘈𝘙𝘐𝘋2, which stands for “Jumonji and AT-Rich Interaction Domain containing 2”: a histone demethylase and member of the α-ketoglutarate-dependent hydroxylase superfamily. /5
Proteins that contain what became known as the Jumonji C (JmjC) domain can remove methyl groups from histone lysine residues. Iron and αKG are required cofactors. These are important epigenetic regulators, influencing gene expression during development and throughout life./6
JmjC aren't the only family of histone demethylases (also called KDMs, colloquially “methylation erasers”). The flavin-dependent lysine demethylases (LSDs or KDM1s) are important too. Deregulation of these histone erasers is one of the most common alterations in human cancer./7
There are LSD1 modulators in the clinic, but although degraders & inhibitors (mostly αKG-competitve) have been developed for Jumonji demethylases, they aren’t yet being tested in patients quite yet, as summarized in this nice recent @COSB_CRSB review. Now switching gears.../8
Jumanji began with a 1981 book about a magical immersive jungle-themed board game, written & illustrated by author Chris Van Allsburg (depicted with dog). The word Jumanji, Van Allsburg reported, is Zulu and means “many effects.”/9
Like Jumonji, Jumanji had a big year in 1995. The book was made into a movie starring the late Robin Williams, which spawned a real non-magical board game, a late 1990s animated TV series, the space-themed spinoff “Zathura”, and a 2017 Dwyane Johnson reboot and sequel./10
Van Allsburg is best known for Polar Express, but our kids liked The Mysteries of Harris Burdick. It's a weird book – one page has an image of a nun sitting in a chair floating in a cathedral, with the text, ‘THE SEVEN CHAIRS: The fifth one ended up in France.” No explanation./11
That's it. If you're still confused about Jumanji and Jumonji, Wikipedia has a helpful disambiguation page. And don't worry - your cells know the difference. 😀/12End #HematologyTweetstory #Jumanji #Jumonji