| First Author | Nakashima A | Year | 2018 |
| Journal | Hypertension | Volume | 72 |
| Issue | 3 | Pages | 746-754 |
| PubMed ID | 30012868 | Mgi Jnum | J:271702 |
| Mgi Id | MGI:6282958 | Doi | 10.1161/HYPERTENSIONAHA.118.11075 |
| Citation | Nakashima A, et al. (2018) Dec1 and CLOCK Regulate Na(+)/K(+)-ATPase beta1 Subunit Expression and Blood Pressure. Hypertension 72(3):746-754 |
| abstractText | Blood pressure shows a circadian rhythm, and recent studies have suggested the involvement of a molecular clock system in its control. In the clock system, the CLOCK (circadian locomotor output cycles kaput):BMAL1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1) heterodimer enhances promoter activity of clock genes, and DEC1 (BHLHE40/STRA13/SHARP-2) represses CLOCK/BMAL1-enhanced promoter activity through competition for binding to the clock element, CACGTG E-box. However, the molecular mechanisms by which this system regulates blood pressure remain unclear. Here, we show that DEC1 suppressed the expression of ATP1B1, which encodes the beta1 subunit of the Na(+)/K(+)-ATPase and elevated blood pressure. Using chromatin immunoprecipitation and chromatin immunoprecipitation-on-chip analyses, we found that DEC1 and CLOCK bound to E-boxes in the ATP1B1 promoter. Luciferase assays revealed that CLOCK:BMAL1 heterodimer enhanced transcription from the ATP1B1 promoter, whereas DEC1 suppressed this transactivation. Accordingly, Atp1b1 mRNA and protein levels in mouse kidney, aorta, and heart showed a circadian rhythm that was antiphasic to the blood pressure rhythm. Furthermore, Dec1-deficient mice showed enhanced Atp1b1 expression in these tissues and reduced blood pressure. In contrast, Clock-mutant mice showed reduced Atp1b1 expression and elevated blood pressure. Our results raise the possibility that transcriptional regulation of Atp1b1 by DEC1 and CLOCK:BMAL1 contributes to blood pressure. |
