Basic—Alimentary TractCircadian Clock-Controlled Intestinal Expression of the Multidrug-Resistance Gene mdr1a in Mice
Section snippets
Materials and Methods
A detailed methods section is provided in the Supplementary Materials (see Supplementary materials online at www.gastrojournal.org).
Transcriptional Regulation of mdr1a Gene by Clock Gene Products
To explore whether products of clock genes regulate expression of the mdr1a gene, we first looked for consensus sequences within the promoter region of the mdr1a gene. Two nucleotide sequences showing homology with the PAR bZIP protein response element (PARRE) RTTAYGYAAY (where R is a purine and Y is a pyrimidine) were found within 1.0 kilobase (kb) of the mdr1a gene 5′-flanking region (Figure 1A). Furthermore, an E-box element CACGTG, consensus-binding site for CLOCK/BMAL1, was also identified
Discussion
PAR bZIP transcription factors DBP, TEF, and HLF have been shown to function as mediators of circadian output physiology. They are expressed in robust circadian fashion in most organs, although the expression of HLF is more restricted to the brain, liver, kidney, and small intestine.30 Recent studies suggested that PAR bZIP proteins and E4BP4 participate in the control of the expression of genes responsible for xenobiotic detoxification, such as cytochrome P450 enzymes, carboxylesterases, and
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Supported, in part, by a grant-in-aid for Scientific Research on Priority Areas “Cancer” from the Ministry of Education, Culture, Sport, Science and Technology (18014020 and 20014016, to S.O.); a grant-in-aid for Scientific Research (B) (18390050, to S.O.); and a grant-in-aid for Encouragement of Young Scientists (18790692, to S.K.) from the Japan Society for the Promotion of Science.
Y.M., S.K., and S.O. equally contributed to this study.
The authors disclose no conflicts.