Editing Suprachiasmatic nucleus (section)

=== Mammals ===
The SCN functions as a circadian biological clock in vertebrates including teleosts, reptiles, birds, and mammals.<ref>{{Cite journal |last1=Patton |first1=Andrew P. |last2=Hastings |first2=Michael H. |date=2018-08-06 |title=The suprachiasmatic nucleus |journal=Current Biology |volume=28 |issue=15 |pages=R816–R822 |doi=10.1016/j.cub.2018.06.052 |issn=1879-0445 |pmid=30086310|s2cid=51933991 |doi-access=free }}</ref> In mammals, the rhythms produced by the SCN are driven by a [[Transcription translation feedback loop|transcription-translation negative feedback loop (TTFL)]] composed of interacting positive and negative transcriptional [[Feedback|feedback loops]].<ref>{{Cite book |last1=Buhr |first1=Ethan D. |last2=Takahashi |first2=Joseph S. |title=Circadian Clocks |chapter=Molecular Components of the Mammalian Circadian Clock |date=2013 |series=Handbook of Experimental Pharmacology |volume=217 |issue=217 |pages=3–27 |doi=10.1007/978-3-642-25950-0_1 |issn=0171-2004 |pmc=3762864 |pmid=23604473|isbn=978-3-642-25949-4 }}</ref><ref>{{Cite journal |last1=Shearman |first1=Lauren P. |last2=Sriram |first2=Sathyanarayanan |last3=Weaver |first3=David R. |last4=Maywood |first4=Elizabeth S. |last5=Chaves |first5=Inẽs |last6=Zheng |first6=Binhai |last7=Kume |first7=Kazuhiko |last8=Lee |first8=Cheng Chi |last9=Der |first9=Gijsbertus T. J. van |last10=Horst |last11=Hastings |first11=Michael H. |last12=Reppert |first12=Steven M. |date=2000 |title=Interacting Molecular Loops in the Mammalian Circadian Clock |url=https://www.academia.edu/15431872 |journal=Science |volume=288 |issue=5468 |pages=1013–1019 |doi=10.1126/science.288.5468.1013 |pmid=10807566 |bibcode=2000Sci...288.1013S |issn=0036-8075}}</ref><ref name="Reppert 935–941">{{Cite journal |last1=Reppert |first1=Steven M. |last2=Weaver |first2=David R. |date=2002-08-29 |title=Coordination of circadian timing in mammals |url=https://pubmed.ncbi.nlm.nih.gov/12198538/ |journal=Nature |volume=418 |issue=6901 |pages=935–941 |doi=10.1038/nature00965 |issn=0028-0836 |pmid=12198538|bibcode=2002Natur.418..935R |s2cid=4430366 }}</ref> Within the nucleus of an SCN cell, the genes ''Clock'' and ''Bmal1 (mop3)'' encode the [[Basic helix–loop–helix|BHLH]]-[[PAS domain|PAS]] [[transcription factor]]s [[CLOCK]] and [[ARNTL|BMAL1 (MOP3)]], respectively. CLOCK and BMAL1 are positive [[Activator (genetics)|activators]] that form CLOCK-BMAL1 [[Protein dimer|heterodimers]]. These heterodimers then bind to [[E-box]]es upstream of multiple genes, including ''per'' and ''cry'', to enhance and promote their [[Transcription (biology)|transcription]] and eventual [[Translation (biology)|translation]].<ref name=":6">{{Cite journal |last1=Gekakis |first1=N. |last2=Staknis |first2=D. |last3=Nguyen |first3=H. B. |last4=Davis |first4=F. C. |last5=Wilsbacher |first5=L. D. |last6=King |first6=D. P. |last7=Takahashi |first7=J. S. |last8=Weitz |first8=C. J. |date=1998-06-05 |title=Role of the CLOCK protein in the mammalian circadian mechanism |url=https://pubmed.ncbi.nlm.nih.gov/9616112/ |journal=Science |volume=280 |issue=5369 |pages=1564–1569 |doi=10.1126/science.280.5369.1564 |issn=0036-8075 |pmid=9616112|bibcode=1998Sci...280.1564G }}</ref><ref name="Reppert 935–941"/> In mammals, there are three known [[Sequence homology|homologs]] for the ''[[Period (gene)|period]]'' gene in ''[[Drosophila]]'', namely ''[[PER1|per1]]'', ''[[PER2|per2]]'', and ''[[PER3|per3]]''.

As ''per'' and ''cry'' are transcribed and translated into PER and CRY, the proteins accumulate and form heterodimers in the cytoplasm. The heterodimers are [[Protein phosphorylation|phosphorylated]] at a rate that determines the length of the transcription-translation feedback loop (TTFL) and then translocate back into the nucleus where the phosphorylated PER-CRY heterodimers act on CLOCK and/or BMAL1 to inhibit their activity. Although the role of phosphorylation in the TTFL mechanism is known, the specific kinetics are yet to be elucidated.<ref>{{Cite journal |last1=Herzog |first1=Erik D. |last2=Hermanstyne |first2=Tracey |last3=Smyllie |first3=Nicola J. |last4=Hastings |first4=Michael H. |date=2017-01-03 |title=Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms |journal=Cold Spring Harbor Perspectives in Biology |volume=9 |issue=1 |pages=a027706 |doi=10.1101/cshperspect.a027706 |issn=1943-0264 |pmc=5204321 |pmid=28049647}}</ref> As a result, PER and CRY function as negative [[repressor]]s and inhibit the transcription of ''per'' and ''cry''. Over time, the PER-CRY heterodimers degrade and the cycle begins again with a period of about 24.5 hours.<ref>{{Cite journal |last1=Kume |first1=K. |last2=Zylka |first2=M. J. |last3=Sriram |first3=S. |last4=Shearman |first4=L. P. |last5=Weaver |first5=D. R. |last6=Jin |first6=X. |last7=Maywood |first7=E. S. |last8=Hastings |first8=M. H. |last9=Reppert |first9=S. M. |date=1999-07-23 |title=mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop |journal=Cell |volume=98 |issue=2 |pages=193–205 |doi=10.1016/s0092-8674(00)81014-4 |issn=0092-8674 |pmid=10428031|s2cid=15846072 |doi-access=free }}</ref><ref>{{Cite journal |last1=Okamura |first1=H. |last2=Miyake |first2=S. |last3=Sumi |first3=Y. |last4=Yamaguchi |first4=S. |last5=Yasui |first5=A. |last6=Muijtjens |first6=M. |last7=Hoeijmakers |first7=J. H. |last8=van der Horst |first8=G. T. |date=1999-12-24 |title=Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock |url=https://pubmed.ncbi.nlm.nih.gov/10617474/ |journal=Science |volume=286 |issue=5449 |pages=2531–2534 |doi=10.1126/science.286.5449.2531 |issn=0036-8075 |pmid=10617474}}</ref><ref>{{Cite journal |last1=Gao |first1=Peng |last2=Yoo |first2=Seung-Hee |last3=Lee |first3=Kyung-Jong |last4=Rosensweig |first4=Clark |last5=Takahashi |first5=Joseph S. |last6=Chen |first6=Benjamin P. |last7=Green |first7=Carla B. |date=2013-12-06 |title=Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian period length |journal=The Journal of Biological Chemistry |volume=288 |issue=49 |pages=35277–35286 |doi=10.1074/jbc.M113.509604 |issn=1083-351X |pmc=3853276 |pmid=24158435 |doi-access=free }}</ref><ref name="Reppert 935–941"/><ref>{{Cite journal |last1=Matsumura |first1=Ritsuko |last2=Tsuchiya |first2=Yoshiki |last3=Tokuda |first3=Isao |last4=Matsuo |first4=Takahiro |last5=Sato |first5=Miho |last6=Node |first6=Koichi |last7=Nishida |first7=Eisuke |last8=Akashi |first8=Makoto |date=2014-11-14 |title=The mammalian circadian clock protein period counteracts cryptochrome in phosphorylation dynamics of circadian locomotor output cycles kaput (CLOCK) |journal=The Journal of Biological Chemistry |volume=289 |issue=46 |pages=32064–32072 |doi=10.1074/jbc.M114.578278 |issn=1083-351X |pmc=4231683 |pmid=25271155 |doi-access=free }}</ref> The integral genes involved, termed “clock genes," are highly conserved throughout both SCN-bearing vertebrates like mice, rats, and birds as well as in non-SCN bearing animals such as ''Drosophila''.<ref>{{Cite journal |last=Cassone |first=Vincent M. |date=January 2014 |title=Avian circadian organization: a chorus of clocks |journal=Frontiers in Neuroendocrinology |volume=35 |issue=1 |pages=76–88 |doi=10.1016/j.yfrne.2013.10.002 |issn=1095-6808 |pmc=3946898 |pmid=24157655}}</ref>