A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle, indicating that properly timed gene expression is important for regulating cell-cycle events. Genomic analyses of the localization and expression dynamics of transcription factors suggest that a network of sequentially expressed transcription factors could control the temporal programme of transcription during the cell cycle3. However, directed studies interrogating small numbers of genes indicate that their periodic transcription is governed by the activity of cyclin-dependent kinases (CDKs)4. To determine the extent to which the global cell-cycle transcription programme is controlled by cyclin–CDK complexes, we examined genome-wide transcription dynamics in budding yeast mutant cells that do not express S-phase and mitotic cyclins. Here we show that a significant fraction of periodic genes are aberrantly expressed in the cyclin mutant. Although cells lacking cyclins are blocked at the G1/S border, nearly 70% of periodic genes continued to be expressed periodically and on schedule. Our findings reveal that although CDKs have a function in the regulation of cell-cycle transcription, they are not solely responsible for establishing the global periodic transcription programme. We propose that periodic transcription is an emergent property of a transcription factor network that can function as a cell-cycle oscillator independently of, and in tandem with, the CDK oscillator. Helikar Tomas thelika@unmc.edu University of Nebraska - Lincoln 2015-02-05T09:45:30Z 2016-01-22T07:08:46Z

<font face="Georgia" style="font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal; font-family: Arial, Verdana;"><span style="font-style: normal; line-height: 16px; background-color: rgb(255, 255, 255);">G1/S-specific cyclin CLN3 (</span><i style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">Saccharomyces cerevisiae</i><i style="font-style: normal; line-height: 19.1875px; background-color: rgb(255, 255, 255);">)</i></font><div style="font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal; font-family: Arial, Verdana;"><font face="Georgia"><span style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">UniProt ID:</span><i style="font-style: normal; line-height: 19.1875px; background-color: rgb(255, 255, 255);"> </i><span style="font-style: normal; background-color: rgb(255, 255, 255);">P13365</span></font></div><div style="font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal; font-family: Arial, Verdana;"><font face="Georgia"><span style="font-style: normal; background-color: rgb(255, 255, 255);"><br/></span></font></div><div>For Budding Yeast Cell Cycle 2009:</div><div>Cln3 includes the following genes, proteins, events:</div><div><br/></div><div>Cln3</div><div>UniProt ID: P13365</div><div><br/></div><div>Cln3-Cdc28</div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P00546" style="border-bottom-width: 0px; cursor: pointer;">P00546</a></div><div><br/></div><div>Bck2:</div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P33306" style="border-bottom-width: 0px; cursor: pointer;">P33306</a></div>

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<div><span style="color: rgb(84, 84, 84); font-family: arial, sans-serif; font-size: small; line-height: 18.2000007629395px; background-color: rgb(255, 255, 255);">AngiotensinI-converting enzyme 2 (</span><span style="font-weight: bold; color: rgb(84, 84, 84); font-family: arial, sans-serif; font-size: small; line-height: 18.2000007629395px; background-color: rgb(255, 255, 255);">ACE 2</span><span style="color: rgb(84, 84, 84); font-family: arial, sans-serif; font-size: small; line-height: 18.2000007629395px; background-color: rgb(255, 255, 255);">)</span></div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P21192" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">P21192</a></div><div>Gene Name: ACE2</div><div>Gene ID: <span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">59272</span></div>

2015-11-15T20:53:08Z

<strong style="font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; font-style: normal; font-variant: normal; font-weight: normal; line-height: 20.081974029541px; color: rgb(68, 68, 68); background-color: rgb(255, 255, 255);">Forkhead transcription factor HCM1</strong><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P25364" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">P25364</a></div><div>Gene Name: hcm1</div><div>Gene ID: <span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">4851769</span></div>

2015-11-15T20:53:08Z

<span style="font-style: normal; line-height: 17px; background-color: rgb(255, 255, 255);"><font face="Georgia">SBF is a heterodimer of Swi4 and Swi6. </font></span><div><ul><li><span style="font-family: Georgia; line-height: 16px; background-color: rgb(255, 255, 255);">Regulatory protein SWI4 (</span><span style="font-family: Georgia; line-height: 19.1875px; background-color: rgb(255, 255, 255);">Saccharomyces cerevisiae</span><span style="font-family: Georgia; line-height: 19.1875px; background-color: rgb(255, 255, 255);">), UniProt ID: </span><span style="font-family: Georgia; background-color: rgb(255, 255, 255);">P25302</span></li><li><span style="font-family: Georgia; line-height: 16px; background-color: rgb(255, 255, 255);">Regulatory protein SWI6 (</span><i style="font-family: Georgia; line-height: 19.1875px; background-color: rgb(255, 255, 255);">Saccharomyces cerevisiae</i><span style="font-family: Georgia; line-height: 19.1875px; background-color: rgb(255, 255, 255);">), UniProt ID: </span><span style="font-family: Georgia; background-color: rgb(255, 255, 255);">P09959</span></li></ul></div>

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<div>Homeobox protein YOX1</div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P34161" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">P34161</a><div>Gene Name: YOX1</div><div>Gene ID: <span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">854981</span></div>

2015-11-15T20:53:08Z

<font face="Arial, Verdana" size="2">Represents the yeast cell cycle transcription factor: Swi Five Factor [1]. </font><div><br/></div><div>Transcript factor complex including: Fkh2 and Ndd1 [2]</div><div><br/></div><div>Nuclear division defective protein 1</div><div>Uniprot AccessionID: <a href="http://www.uniprot.org/uniprot/Q08887" style="border-bottom-width: 0px; cursor: pointer;">Q08887</a></div><div><br/></div><div>Fork head protein homolog 2</div><div>UniProt AccessionID: <a href="http://www.uniprot.org/uniprot/P41813" style="border-bottom-width: 0px; cursor: pointer;">P41813</a></div>

2015-11-15T20:53:08Z

<font face="Georgia"><span style="font-style: normal; line-height: 16px; background-color: rgb(255, 255, 255);">Transcriptional factor SWI5 (</span><i style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">Saccharomyces cerevisiae</i><i style="font-style: normal; line-height: 19.1875px; background-color: rgb(255, 255, 255);">)</i></font><div><font face="Georgia"><span style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">P08153</span></font></div>

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<div style="font-style: normal;"><span style="line-height: 17px; background-color: rgb(255, 255, 255);"><font face="Georgia">MBF is a heterodimer of Mbpl and Swi6 [1]:</font></span></div><font face="Georgia"></font><ul><li><font face="Georgia"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Transcription factor MBP1</span><span style="line-height: 16px; background-color: rgb(255, 255, 255);"> (</span><i style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">Saccharomyces cerevisiae</i><span style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">), </span></font><span style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">UniProt ID:</span><span style="line-height: 19.1875px; background-color: rgb(255, 255, 255);"> </span><span style="background-color: rgb(255, 255, 255);">P39678</span></li><li><font face="Georgia"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Regulatory protein SWI6 (</span><i style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">Saccharomyces cerevisiae</i><span style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">), </span></font><span style="line-height: 19.1875px; background-color: rgb(255, 255, 255);">UniProt ID:</span><span style="background-color: rgb(255, 255, 255);">P09959</span></li></ul>

2015-11-15T20:53:08Z

Homeobox protein<strong style="font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; font-style: normal; font-variant: normal; font-weight: normal; line-height: 20.081974029541px; color: rgb(68, 68, 68); background-color: rgb(255, 255, 255);"> </strong><font face="Georgia" size="2" style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Yhp1p [</span><em style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Saccharomyces cerevisiae S288c</em><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">]</span></font><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q04116" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q04116</a></font></div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/852062" ref="ordinalpos=1&ncbi_uid=852062&link_uid=852062" style="line-height: 17.999801635742188px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">YHP1</span></a></font></div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">NCBI Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 16.19982147216797px;">852062</span></font></div>

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<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">ACE2 activates CLN3 [1, 2]. </span><span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">SWI5 activates CLN3 [1, 3]. </span><span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">YHP1 inhibits CLN3 [1, 4]. </span><span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 13.3333330154419px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">YOX1 inhibits CLN3 [1, 4]</span>

<span style="font-size: 13.3333330154419px;">YOX1 inhibits CLN3 [1, 4]</span>

SWI5 activates CLN3 [1, 3]

ACE2 activates CLN3 [1, 2]

YHP1 inhibits CLN3 [1, 4]

S_7 1 S_2 1 S_9 1 S_5 1

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">SFF activates ACE2 [1]</span>

SFF activates ACE2 [1]

S_6 1

<span style="font-size: 13.3333330154419px;">MBF activates HCM1 [1]. S</span><span style="font-size: 13.3333330154419px;">BF activates HCM1 [1]</span>

MBF activates HCM1 [1]

<span style="font-size: 13.3333330154419px;">SBF activates HCM1 [1]</span>

S_8 1 S_4 1

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">MBF activates SBF [1]. </span><span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">CLN3 activates SBF [1, 2, 3]. </span><span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">YHP1 inhibits SBF [1]. </span><span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">YOX1 inhibits SBF [1].</span>

MBF activates SBF [1]

<span style="font-size: 13.3333330154419px;">YOX1 inhibits SBF [1]</span>

YHP1 inhibits SBF [1]

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> Cln3 is known to directly inhibit Whi5 and thereby activate MBF and SBF complexes [1, 2, 3]</span>

S_8 1 S_9 1 S_5 1 S_1 1 S_9 1 S_5 1

MBF activates YOX1 [1, 2, 3, 4, 5]. SBF activates YOX1 [1].

A portion of the MBF complex, MBP1, activates YOX1 [1, 2, 3, 4, 5]

SBF activates YOX1 [1]

S_8 1 S_4 1

<span style="font-size: 13.3333330154419px;">HCM1 activates SFF [1]. </span><span style="font-size: 13.3333330154419px;">SBF activates SFF [1].</span>

HCM1 activates SFF [1]

<span style="font-size: 13.3333330154419px;">SBF activates SFF [1]</span>

S_4 1 S_3 1

SFF activates SWI5 [1].

<span style="font-size: 13.3333330154419px;">SFF activates SWI5 [1]</span>

S_6 1

MBF is positively regulated by CLN3 [1, 2, 3].

 Cln3 is known to directly\r\ninhibit Whi5 and thereby activate MBF and SBF complexes [1, 2, 3]

S_1 1

<span style="font-size: 13.3333330154419px;">SBF activates YHP1 [1]. MBF activates YHP1 [1, 2, 3, 4, 5].</span>

A portion of the MBF complex, MBP1, activates YHP1 [1, 2, 3, 4, 5]

SBF activates YHP1 [1]

S_4 1 S_8 1