title: Regulation of large-scale chromatin unfolding by Smad4.
abstract: 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.
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, PR China. yeqn@nic.bmi.ac.cn
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.forename: Lihua
authors.initials: L
authors.lastname: Ding
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.forename: Qiujun
authors.initials: Q
authors.lastname: Lu
authors.forename: Cuifen
authors.initials: C
authors.lastname: Huang
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
mesh_terms: 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
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D008156:Luciferases