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- Title
Clock and Light Regulation of the CREB Coactivator CRTC1 in the Suprachiasmatic Circadian Clock.
- Authors
Sakamoto, Kensuke; Norona, Frances E.; Alzate-Correa, Diego; Scarberry, Daniel; Hoyt, Kari R.; Obrietan, Karl
- Abstract
The CREB/CRE transcriptional pathway has been implicated in circadian clock timing and light-evoked clock resetting. To date, much of the work on CREB in circadian physiology has focused on how changes in the phosphorylation state of CREB regulate the timing processes. However, beyond changes in phosphorylation, CREB-dependent transcription can also be regulated by the CREB coactivator CRTC (CREB-regulated transcription coactivator), also known as TORC (transducer of regulated CREB). Here we profiled both the rhythmic and light-evoked regulation of CRTC1 and CRTC2 in the murine suprachiasmatic nucleus (SCN), the locus of the master mammalian clock. Immunohistochemical analysis revealed rhythmic expression of CRTC1 in the SCN. CRTC1 expression was detected throughout the dorsoventral extent of the SCN in the middle of the subjective day, with limited expression during early night, and late night expression levels intermediate between mid-day and early night levels. In contrast to CRTC1, robust expression of CRTC2 was detected during both the subjective day and night. During early and late subjective night, a brief light pulse induced strong nuclear accumulation of CRTC1 in the SCN. In contrast with CRTC 1, photic stimulation did not affect the subcellular localization of CRTC2 in the SCN. Additionally, reporter gene profiling and chromatin immunoprecipitation analysis indicated that CRTC1 was associated with CREB in the 5' regulatory region of the periodl gene, and that overexpression of CRTC1 leads to a marked upregulation in periodl transcription. Together, these data raise the prospect that CRTC1 plays a role in fundamental aspects of SCN clock timing and entrainment.
- Subjects
TRANSCRIPTION factors; CIRCADIAN rhythms; SUPRACHIASMATIC nucleus; PHOSPHORYLATION; IMMUNOHISTOCHEMISTRY; GENE expression
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 21, p9021
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4202-12.2013