Fig. 3.

NO66 is implicated in skeletal development and tumorigenesis. a NO66 represses the osteoblast-specific transcription factor Osterix (Osx). Osterix drives the transcription of specific target genes (e.g., Col1a1) to promote osteoblast differentiation and bone development. The dimerization domain of NO66 interacts with the transactivation domain of Osx, leading to reduced Osx target gene expression. Whether this involves a direct effect of an NO66 histone demethylase activity, or results from the recruitment of multiple epigenetic modifiers (e.g., PRC2, HP1, etc.), is currently unclear (signified by ‘?’). b NO66 is over-expressed in lung and colorectal cancers and promotes tumor cell growth and invasion in vitro. Whether the enzymatic activity of NO66 is involved is unclear (‘-OH?’). The molecular mechanisms involved are also unknown, but could be related to roles in myc-driven transcriptional control (left) and/or ribosome biogenesis/translation (right). HDAC1A histone deacetylase 1A; PRC2 polycomb repressor complex 2; HP1 heterochromatin protein 1; DNMT1A DNA methyltransferase 1A; Col1a1 collagen type I alpha 1 chain; Bsp bone sialoprotein; Oc osteocalcin; HAT histone acetyltransferase complex (TRRAP and TIP60)