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A Pineal Regulatory Element (PIRE) Mediates Transactivation by the Pineal/Retina-Specific Transcription Factor CRX
Xiaodong Li, Shiming Chen, Qingliang Wang, Donald J. Zack, Solomon H. Snyder and Jimo Borjigin
Proceedings of the National Academy of Sciences of the United States of America
Vol. 95, No. 4 (Feb. 17, 1998), pp. 1876-1881
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/44378
Page Count: 6
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The circadian hormone melatonin is synthesized predominantly in the pineal gland by the actions of two pineal-specific enzymes: serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). Pineal night-specific ATPase (PINA), another pineal- and night-specific protein we recently identified, is produced as a truncated form of the Wilson disease gene (Atp7b) product. To identify the regulatory elements required for pineal-specific gene expression, we isolated sequences upstream of the rat PINA gene and discovered a cis-acting element that is recognized by a novel pineal/retina-specific nuclear factor. This pineal regulatory element (PIRE) has a consensus of TAATC/T and is present in six copies in the 5′ regulatory region of the PINA gene, at least three copies in the rat NAT promoter, and at least one copy in each of the putative HIOMT promoters A and B. A recently identified retina-specific protein, cone rod homeobox (CRX), binds to PIRE in vitro and transactivates PIRE-reporter constructs. These data suggest that Crx may play a crucial role in regulating pineal gene expression through interactions with PIRE.
Proceedings of the National Academy of Sciences of the United States of America © 1998 National Academy of Sciences