Relationship between circadian oscillations of Rev-erbalpha expression and intracellular levels of its ligand, heme

• Published in: Biochemical and biophysical research communications 2008-04, Vol.368 (4), p.955-958
• Main Authors: Rogers, Pamela M, Ying, Ling, Burris, Thomas P
• Format: Article
• Language: English
• Subjects: Animals; ARNTL Transcription Factors; Basic Helix-Loop-Helix Transcription Factors - biosynthesis; Cell Cycle Proteins - biosynthesis; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; DNA-Binding Proteins - metabolism; Heme - metabolism; Horses; Mice; NIH 3T3 Cells; Nuclear Proteins - biosynthesis; Nuclear Receptor Subfamily 1, Group D, Member 1; Period Circadian Proteins; Receptors, Cytoplasmic and Nuclear - metabolism; Transcription Factors - biosynthesis
• ISSN: 1090-2104
• DOI: 10.1016/j.bbrc.2008.02.031

The nuclear hormone receptors, REV-ERBalpha [NR1D1] and REV-ERBbeta [NR1D1], were recently demonstrated to be receptors for the porphyrin, heme. Heme regulates the ability of these receptors to repress transcription of their target genes via modulation of the affinity of the receptor's ligand binding domain for the corepressor, NCoR. The REV-ERBs function as critical components of the mammalian clock and their expression oscillates in a circadian manner. Here, we show that in NIH3T3 cells intracellular heme levels also oscillate in a circadian fashion. These data are the first to show the temporal relationship of intracellular heme levels to the expression of its receptor, Rev-erbalpha, and suggest that the rapid oscillations in heme levels may an important component regulating REV-ERB transcriptional activity.