Identification and characterization of a novel Schwann and outflow tract endocardial cushion lineage-restricted periostin enhancer.
Periostin is a fasciclin-containing adhesive glycoprotein that facilitates the migration and differentiation of cells that have undergone epithelial-mesenchymal transformation during embryogenesis and in pathological conditions. Despite the importance of post-transformational differentiation as a general developmental mechanism, little is known how periostin's embryonic expression is regulated. To help resolve this deficiency, a 3.9-kb periostin proximal promoter was isolated and shown to drive tissue-specific expression in the neural crest-derived Schwann cell lineage and in a subpopulation of periostin-expressing cells in the cardiac outflow tract endocardial cushions. In order to identify the enhancer and associated DNA binding factor(s) responsible, in vitro promoter dissection was undertaken in a Schwannoma line. Ultimately a 304-bp(peri) enhancer was identified and shown to be capable of recapitulating 3.9 kb(peri-lacZ)in vivo spatiotemporal patterns. Further mutational and EMSA analysis helped identify a minimal 37-bp region that is bound by the YY1 transcription factor. The 37-bp enhancer was subsequently shown to be essential for in vivo 3.9 kb(peri-lacZ) promoter activity. Taken together, these studies identify an evolutionary-conserved YY1-binding 37-bp region within a 304-bp periostin core enhancer that is capable of regulating simultaneous novel tissue-specific periostin expression in the cardiac outflow-tract cushion mesenchyme and Schwann cell lineages.
Lindsley
Andrew
A
Cardiovascular Development Group, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Snider
Paige
P
Zhou
Hongming
H
Rogers
Rhonda
R
Wang
Jian
J
Olaopa
Michael
M
Kruzynska-Frejtag
Agnieszka
A
Koushik
Shrinagesh V
SV
Lilly
Brenda
B
Burch
John B E
JB
Firulli
Anthony B
AB
Conway
Simon J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D015342:DNA Probes / Q000235:genetics; D004699:Endocardium / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005318:Fetal Heart / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D050986:YY1 Transcription Factor / Q000378:metabolism
D015815:Cell Adhesion Molecules; D015342:DNA Probes; C082838:Postn protein, mouse; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse