Abstract
Osterix (Osx) is an osteoblast-specific transcriptional factor and is required for osteoblast differentiation and bone formation. A JmjC domain-containing protein NO66 was previously found to participate in regulation of Osx transcriptional activity and plays an important role in osteoblast differentiation through interaction with Osx. Here, we report the crystal structure of NO66 forming in a functional tetramer. A hinge domain links the N-terminal JmjC domain and C-terminal winged helix-turn-helix domain of NO66, and both domains are essential for tetrameric assembly. The oligomerization interface of NO66 interacts with a conserved fragment of Osx. We show that the hinge domain-dependent oligomerization of NO66 is essential for inhibition of Osx-dependent gene activation. Our findings suggest that homo-oligomerization of JmjC domain containing proteins might play a physiological role through interactions with other regulatory factors during gene expression.
Highlights
A novel JmjC domain-containing protein NO66 has been identified in the regulatory network of Osx
The JmjC domain of NO66 adopts a noncanonical -jellyroll fold composed of seven -strands, in which the second -strand of the canonical -jellyroll folds into an unstructured loop (Fig. 1C)
We report the crystal structure of NO66, a JmjC domain-containing protein, which shows that the fragment lacking the N-terminal 182 amino acid residues bears several unique structural features
Summary
A novel JmjC domain-containing protein NO66 has been identified in the regulatory network of Osx. A JmjC domain-containing protein NO66 was previously found to participate in regulation of Osx transcriptional activity and plays an important role in osteoblast differentiation through interaction with Osx. Here, we report the crystal structure of NO66 forming in a functional tetramer. Our findings suggest that homo-oligomerization of JmjC domain containing proteins might play a physiological role through interactions with other regulatory factors during gene expression. The differentiation of mesenchyme precursors into osteoblasts is regulated by osteoblast-specific transcription factors Runx and osterix (Osx), which play an essential role in osteoblast differentiation and bone formation [2, 3]. Other factors such as histone deacetylases, Twist 1 and 2, ATF4, NFATc, Msx, and Dlx, are involved in the regulation of osteoblast differentiation (4 –7). Regardless of how NO66 catalyzes the reactions, the detailed mechanism for interactions between NO66 and its partners remains unclear
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