Journal
GENOMICS
Volume 79, Issue 3, Pages 278-284Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/geno.2002.6703
Keywords
CASTing; PAX3; Waardenburg; cancer; ARMS; FKHR; EN2; TGFA; VEGF; Itm2A; and BVES
Funding
- NATIONAL CANCER INSTITUTE [R01CA071838, R01CA064202] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [Z01DC000040, Z01DC000039, Z01DC000048] Funding Source: NIH RePORTER
- NCI NIH HHS [R01-CA64202, R01-CA71838] Funding Source: Medline
- NIDCD NIH HHS [1Z01-DC00040-04] Funding Source: Medline
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PAX3 is a transcription factor important for neural, muscle, and facial development in vertebrates. To identify genes regulated by PAX3, we used a cyclic amplification and selection of targets (CASTing) strategy to isolate cis-regulatory elements bound by PAX3. CASTing libraries were constructed with mouse DNA fragments bound by mouse PAX3, and human genomic DNA fragments bound by human PAX3 and the fusion protein PAX3-FKHR. Approximately 1000 clones were sequenced from each of these three libraries. Numerous putative targets of PAX3 and PAX3-FKHR were identified and six genes, Itm2A, Fath, FLT1, TGFA, BVES, and EN2, were examined closely. The genomic DNA fragments near these genes contain PAX3 binding sites and confer PAX3-dependent regulation. The expression levels of these genes correlate with the PAX3 expression levels in mouse embryos or with PAX3-FKHR expression levels in rhabdomyosarcoma cell lines, and indicate they may be part of the PAX3 regulatory circuitry during embryogenesis and tumor formation.
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