Dataset Information

Smad2 and PEA3 cooperatively regulate transcription of response gene to complement 32 in TGF-?-induced smooth muscle cell differentiation of neural crest cells.

ABSTRACT: Response gene to complement 32 (RGC-32) is activated by transforming growth factor- ? (TGF-?) and plays an important role in smooth muscle cell (SMC) differentiation from neural crest Monc-1 cells. The molecular mechanism governing TGF-? activation of RGC-32, however, remains to be determined. The present studies indicate that TGF-? regulates RGC-32 gene transcription. Sequence analysis revealed a Smad binding element (SBE) located in the region from -1344 to -1337 bp upstream of the transcription start site of RGC-32 gene. A polyomavirus enhancer activator (PEA3) binding site is adjacent to the SBE. Mutation at either SBE or PEA3 site significantly inhibited RGC-32 promoter activity. Mutations at both sites completely abolished TGF-?-induced promoter activity. Biochemically, TGF-? stimulated recruitment of Smad2, Smad4, and PEA3 to the RGC-32 promoter, as revealed by gel shift and chromatin immunoprecipitation analyses. Functionally, Smad2, but not Smad3, activated RGC-32 promoter. PEA3 appeared to enhance Smad2 activity. In agreement with their function, Smad2, but not Smad3, physically interacted with PEA3. In TGF-?-induced SMC differentiation of Monc-1 cells, knockdown of Smad2 by short hairpin RNA resulted in downregulation of RGC-32 and SMC marker genes. The downregulation of SMC markers, however, was rescued by exogenously introduced RGC-32. These results demonstrate that Smad2 regulation of RGC-32 transcription is essential for SMC differentiation from neural crest cells.

SUBMITTER: Huang WY

PROVIDER: S-EPMC3154553 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Smad2 and PEA3 cooperatively regulate transcription of response gene to complement 32 in TGF-β-induced smooth muscle cell differentiation of neural crest cells.

Huang Wen-Yan WY Xie Weibing W Guo Xia X Li Fengmin F Jose Pedro A PA Chen Shi-You SY

American journal of physiology. Cell physiology 20110525 2

Response gene to complement 32 (RGC-32) is activated by transforming growth factor- β (TGF-β) and plays an important role in smooth muscle cell (SMC) differentiation from neural crest Monc-1 cells. The molecular mechanism governing TGF-β activation of RGC-32, however, remains to be determined. The present studies indicate that TGF-β regulates RGC-32 gene transcription. Sequence analysis revealed a Smad binding element (SBE) located in the region from -1344 to -1337 bp upstream of the transcripti ...[more]

PMID: 21613609

Similar Datasets

Project description:Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) neural crest induction and migration, and (2) early patterning of tissues adjacent to craniofacial chondrogenic condensations.

Dataset Information

Smad2 and PEA3 cooperatively regulate transcription of response gene to complement 32 in TGF-?-induced smooth muscle cell differentiation of neural crest cells.

Publications

Smad2 and PEA3 cooperatively regulate transcription of response gene to complement 32 in TGF-β-induced smooth muscle cell differentiation of neural crest cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets