Regulation of large-scale chromatin unfolding by Smad4.
The tumor suppressor Smad4 plays a critical role in the transforming growth factor-beta (TGF-beta signaling pathway. Smad4 is an essential component of transcriptional complexes mediating the activation of Smad-dependent target genes. However, how Smad4 regulates various chromosomal events remains unknown. Here, we report that Smad4 induces large-scale chromatin unfolding by targeting Smad4 to an amplified, lac operator-containing chromosome region in mammalian cells. This unfolding activity maps to the subdomains within the transactivation domain of Smad4. Both the N-terminal missense and the C-terminal truncated tumor-derived mutations increased the chromatin unfolding activity of Smad4. These data identify a novel function of Smad4 and suggest that regulation of large-scale chromatin unfolding by Smad4 may be responsible for cancer development.
Yan
Jinghua
J
Beijing Institute of Biotechnology, Beijing 100850, PR China. yeqn@nic.bmi.ac.cn
Fang
Yan
Y
Ding
Lihua
L
Zhu
Jianhua
J
Lu
Qiujun
Q
Huang
Cuifen
C
Yang
Xiao
X
Ye
Qinong
Q
D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry*; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D009369:Neoplasms / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D051901:Smad4 Protein; D015534:Trans-Activators / Q000737:chemistry*; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
D002843:Chromatin; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D008156:Luciferases