A pineal regulatory element (PIRE) mediates transactivation by the pineal/retina-specific transcription factor CRX.

Abstract

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.

• Authors: X Li, S Chen, Q Wang, D J Zack, S H Snyder, J Borjigin
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 4 Pg. 1876-81 (Feb 17 1998) ISSN: 0027-8424 [Print] United States
• PMID: 9465110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Cation Transport Proteins
• DNA-Binding Proteins
• Homeodomain Proteins
• Trans-Activators
• cone rod homeobox protein
• Acetylserotonin O-Methyltransferase
• Arylamine N-Acetyltransferase
• Adenosine Triphosphatases
• Copper-Transporting ATPases

Topics

• Acetylserotonin O-Methyltransferase (genetics)
• Adenosine Triphosphatases (genetics)
• Animals
• Arylamine N-Acetyltransferase (genetics)
• Base Sequence
• Carrier Proteins (genetics)
• Cation Transport Proteins
• Circadian Rhythm
• Copper-Transporting ATPases
• DNA-Binding Proteins (metabolism)
• Gene Expression Regulation, Enzymologic
• Homeodomain Proteins (physiology)
• Introns
• Male
• Molecular Sequence Data
• Pineal Gland (physiology)
• Promoter Regions, Genetic
• Rats
• Rats, Sprague-Dawley
• Regulatory Sequences, Nucleic Acid
• Retina (physiology)
• Trans-Activators (physiology)
• Transcription, Genetic
• Transcriptional Activation