Editing Cell cycle (section)

===Transcriptional regulatory network===
Current evidence suggests that a semi-autonomous transcriptional network acts in concert with the CDK-cyclin machinery to regulate the cell cycle. Several gene expression studies in ''[[Saccharomyces cerevisiae]]'' have identified 800–1200 genes that change expression over the course of the cell cycle.<ref name="pmid9843569" /><ref name="pramilaetal2006">{{cite journal | vauthors = Pramila T, Wu W, Miles S, Noble WS, Breeden LL | title = The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle | journal = Genes & Development | volume = 20 | issue = 16 | pages = 2266–2278 | date = August 2006 | pmid = 16912276 | pmc = 1553209 | doi = 10.1101/gad.1450606 }}</ref><ref name="orlandoeta1nature2008">{{cite journal | vauthors = Orlando DA, Lin CY, Bernard A, Wang JY, Socolar JE, Iversen ES, Hartemink AJ, Haase SB | display-authors = 6 | title = Global control of cell-cycle transcription by coupled CDK and network oscillators | journal = Nature | volume = 453 | issue = 7197 | pages = 944–947 | date = June 2008 | pmid = 18463633 | pmc = 2736871 | doi = 10.1038/nature06955 | bibcode = 2008Natur.453..944O }}</ref> They are transcribed at high levels at specific points in the cell cycle, and remain at lower levels throughout the rest of the cycle. While the set of identified genes differs between studies due to the computational methods and criteria used to identify them, each study indicates that a large portion of yeast genes are temporally regulated.<ref name="deLichtenberg2005">{{cite journal | vauthors = de Lichtenberg U, Jensen LJ, Fausbøll A, Jensen TS, Bork P, Brunak S | title = Comparison of computational methods for the identification of cell cycle-regulated genes | journal = Bioinformatics | volume = 21 | issue = 7 | pages = 1164–1171 | date = April 2005 | pmid = 15513999 | doi = 10.1093/bioinformatics/bti093 | doi-access = free }}</ref>

Many periodically expressed genes are driven by [[transcription factor]]s that are also periodically expressed. One screen of single-gene knockouts identified 48 transcription factors (about 20% of all non-essential transcription factors) that show cell cycle progression defects.<ref name="whiteetal2009">{{cite journal | vauthors = White MA, Riles L, Cohen BA | title = A systematic screen for transcriptional regulators of the yeast cell cycle | journal = Genetics | volume = 181 | issue = 2 | pages = 435–446 | date = February 2009 | pmid = 19033152 | pmc = 2644938 | doi = 10.1534/genetics.108.098145 }}</ref> Genome-wide studies using high throughput technologies have identified the transcription factors that bind to the promoters of yeast genes, and correlating these findings with temporal expression patterns have allowed the identification of transcription factors that drive phase-specific gene expression.<ref name="pramilaetal2006" /><ref name="leeetal2002">{{cite journal | vauthors = Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, Zeitlinger J, Jennings EG, Murray HL, Gordon DB, Ren B, Wyrick JJ, Tagne JB, Volkert TL, Fraenkel E, Gifford DK, Young RA | display-authors = 6 | title = Transcriptional regulatory networks in Saccharomyces cerevisiae | journal = Science | volume = 298 | issue = 5594 | pages = 799–804 | date = October 2002 | pmid = 12399584 | doi = 10.1126/science.1075090 | s2cid = 4841222 | bibcode = 2002Sci...298..799L }}</ref> The expression profiles of these transcription factors are driven by the transcription factors that peak in the prior phase, and computational models have shown that a CDK-autonomous network of these transcription factors is sufficient to produce steady-state oscillations in gene expression).<ref name="orlandoeta1nature2008" /><ref name="simonetal2001">{{cite journal | vauthors = Simon I, Barnett J, Hannett N, Harbison CT, Rinaldi NJ, Volkert TL, Wyrick JJ, Zeitlinger J, Gifford DK, Jaakkola TS, Young RA | display-authors = 6 | title = Serial regulation of transcriptional regulators in the yeast cell cycle | journal = Cell | volume = 106 | issue = 6 | pages = 697–708 | date = September 2001 | pmid = 11572776 | doi = 10.1016/S0092-8674(01)00494-9 | s2cid = 9308235 | doi-access = free }}</ref>

Experimental evidence also suggests that gene expression can oscillate with the period seen in dividing wild-type cells independently of the CDK machinery. Orlando ''et al.'' used [[microarray]]s to measure the expression of a set of 1,271 genes that they identified as periodic in both wild type cells and cells lacking all S-phase and mitotic cyclins (''clb1,2,3,4,5,6''). Of the 1,271 genes assayed, 882 continued to be expressed in the cyclin-deficient cells at the same time as in the wild type cells, despite the fact that the cyclin-deficient cells arrest at the border between [[G1 phase|G<sub>1</sub>]] and [[S phase]]. However, 833 of the genes assayed changed behavior between the wild type and mutant cells, indicating that these genes are likely directly or indirectly regulated by the CDK-cyclin machinery. Some genes that continued to be expressed on time in the mutant cells were also expressed at different levels in the mutant and wild type cells. These findings suggest that while the transcriptional network may oscillate independently of the CDK-cyclin oscillator, they are coupled in a manner that requires both to ensure the proper timing of cell cycle events.<ref name="orlandoeta1nature2008" /> Other work indicates that [[phosphorylation]], a post-translational modification, of cell cycle transcription factors by [[Cdk1]] may alter the localization or activity of the transcription factors in order to tightly control timing of target genes.<ref name="whiteetal2009" /><ref name="sidorova1995">{{cite journal | vauthors = Sidorova JM, Mikesell GE, Breeden LL | title = Cell cycle-regulated phosphorylation of Swi6 controls its nuclear localization | journal = Molecular Biology of the Cell | volume = 6 | issue = 12 | pages = 1641–1658 | date = December 1995 | pmid = 8590795 | pmc = 301322 | doi = 10.1091/mbc.6.12.1641 }}</ref><ref name="ubersaxetal2003">{{cite journal | vauthors = Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM, Morgan DO | display-authors = 6 | title = Targets of the cyclin-dependent kinase Cdk1 | journal = Nature | volume = 425 | issue = 6960 | pages = 859–864 | date = October 2003 | pmid = 14574415 | doi = 10.1038/nature02062 | s2cid = 4391711 | bibcode = 2003Natur.425..859U }}</ref>

While oscillatory transcription plays a key role in the progression of the yeast cell cycle, the CDK-cyclin machinery operates independently in the early embryonic cell cycle. Before the [[midblastula transition]], [[zygote|zygotic]] transcription does not occur and all needed proteins, such as the B-type cyclins, are translated from maternally loaded [[mRNA]].<ref name="davidmorganbook2007">{{cite book | vauthors = Morgan DO | title = The Cell Cycle: Principles of Control | publisher = New Science Press | location = London | year = 2007 | pages = 18 | chapter = 2–3 | isbn = 978-0-9539181-2-6 }}</ref>