Lysine Specific Demethylase 6B (KDM6B)

JMJD3, UTX, and UTY comprise a subfamily of JmjC domain-containing proteins that are evolutionarily conserved from C. elegans to human. JMJD3 contains a treble clef zinc finger at the C terminus that is also present in the other family members, but lacks the tetratricopeptide repeats, predicted to be protein interaction domains, in the N-terminal regions present in UTX and UTY. The H3K27me3 marks were removed during calcium-induced differentiation in human keratinocytes in concert with the binding of JMJD3 and loss of SUZ12. Expression of active JMJD3 induced premature epidermal differentiation, as did depletion of SUZ12 or EZH2. In contrast, JMJD3 depletion by small interfering RNA or expression of demethylase-defective JMJD3 mutant prevented normal induction of epidermal differentiation.