Identification of phylogenetically conserved enhancer elements implicated in pancreas development in the WISP1 and CTGF orthologs.
WISP1 and CTGF are members of the CCN family of growth factors encoding extracellular matrix proteins participating in several developmental and tumorigenic processes. Both are induced by the WNT signaling pathway, and microarray data suggest that expression of WISP1 and CTGF is repressed by Neurogenin3 (Ngn3 (NEUROG3)), a transcription factor directing specification of the endocrine pancreas. Single-cell reverse transcription polymerase chain reaction analysis suggested that this was a cell autonomous effect. To identify possible common regulatory networks involved in WISP1 and CTGF gene expression, their genomic regions were searched for common transcription factor motifs using a combination of in silico approaches and documented knowledge concerning pancreas development. This analysis revealed the presence of a conserved enhancer in both CTGF and WISP1 regulatory regions in 10 species covering a wide evolutionary distance. This enhancer contains binding sites for Ngn1/3 (NEUROG1/3) and transcription factors that are critically involved in pancreas development. Furthermore, it contained binding sites for three additional transcription factor families, which may indicate novel players are involved in this process.
Kapasa
M
M
Developmental Biology Laboratory, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.
Serafimidis
I
I
Gavalas
A
A
Kossida
S
S
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D055511:CCN Intercellular Signaling Proteins; D019295:Computational Biology; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010179:Pancreas / Q000254:growth & development* / Q000378:metabolism; D010802:Phylogeny; D011518:Proto-Oncogene Proteins; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051792:Basic Helix-Loop-Helix Proteins; D055511:CCN Intercellular Signaling Proteins; D055513:Connective Tissue Growth Factor; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C492067:CCN4 protein, mouse; C407737:Neurog3 protein, mouse