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Fig. 6. Shn proteins contribute to Bmp signaling by functioning as scaffolding
factors. Shn proteins provide a framework that integrates Smads,
co-activators/co-repressors and other transcription factors. The large size of
Shn proteins may provide the flexibility to recognize different partners and
to act through a variety of cis-elements. On genes such as Xvent2, Id3,
brk, bam and gsb, that contain the GRCKNC(N5)GTCTG consensus,
Smad1/Mad and Smad4/Med bind to GRCKNC and GTCT sites, probably as a
heterotrimeric complex (Gao et al.,
2005) (not represented in this figure). Shn/Shn1 interaction with
the MH2 domains of Smads could stabilize the complex and provide docking sites
for cell/tissue-specific co-repressors, as in A, or co-activators, as
in B. Shn binding in A and B is highly sensitive to the spacing between
the Smad sites indicating steric constraints
(Gao et al., 2005;
Pyrowolakis et al., 2004).
(C) Shn promotes activation of Ubx in the Drosophila
midgut through a promoter element that contains sites for Mad and an
NF
B-like site directly bound by Shn. In this context, there is no
apparent requirement for Med binding to DNA. (D) In contrast, the mouse
PPAR
enhancer that is activated by Shn2 requires sites for Smad4 and
C/EBP
, but does not contain Smad1 motifs
(Jin et al., 2006). The
sensitivity of these enhancers to alterations in spacing between binding sites
has not been tested.
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