Cryptochrome 1 functions as nuclear co-receptor independence of circadian clock

Abstract

Cryptochrome 1 (CRY1) is well known as a circadian clock repressor. Recent studies have shown that it could intimately associate with nuclear receptors and either activate or inhibit its targets at the transcriptional level. In the present study, we applied publicly available transcriptional factors Chromatin Immunoprecipitation coupled high throughput sequencing data to prove that CRY1 associates with various nuclear receptors at the genome-wide level, which is independent of its canonical role as a circadian clock repressor. Furthermore, we have also shown that CRY1 is a confident co-receptor of retinoid X receptor, alpha (RXRa). We have also further shown that CRY1 could directly interact with RXRa. The interaction was regulated by retinoic acid treatment in a dose-dependent manner. In addition, CRY activator could antagonized RA-medicated PCK1 and G6PC expression, which in turn antagonize glucose production. Our findings indicate that CRYs could be potential targets in relieving side effects of RA-oriented treatment for diseases such as leukemia, acne, and psoriasis.