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. Author manuscript; available in PMC: 2013 Mar 2.
Published in final edited form as: Crit Rev Eukaryot Gene Expr. 2012;22(3):205–218. doi: 10.1615/critreveukargeneexpr.v22.i3.40

FIGURE 3.

FIGURE 3

Nmp4/CIZ is a repressive transcription factor that binds near an epigenetic remodeling site in the PTH response region of the Mmp13 promoter. (a) The region in the Mmp13 promoter that regulates response to PTH is conserved in mice, rats, and humans. Nmp4/CIZ binds to this region in a sequence-specific fashion between (−119/−110bp).77 The distal Runx2 site binds to HDAC4 and mediates suppression of Mmp13 transcription. Whether Nmp4 binds to Runx2 or HDAC4 is not yet known. PTH removes HDAC4 as part of the transcription induction mechanism. 78 (b) Introducing null-binding mutations in the Nmp4/CIZ-binding site within the Mmp13 promoter-reporter construct containing the first 1329nt of the 5′-regulatory region and transfected into UMR 106-01 osteoblast-like cells enhances PTH-stimulated transcription induction. Mutating the distal Runx2 site does not significantly alter PTH response, but mutating both the Runx2 and Nmp4 sites dramatically increases hormone-induced transcription (see Ref. 77).