The effects of SN Ps in the regions of positioning RNA polymerase II on the TBP/promoter affinity in the genes of human circadian clock

Genetic variability in the genes of circadian clock is manifested as the phenotypic variability of physiological functions and behavior as well as disorders of the function of not only the clock but also other systems, leading to the development of a pathologies. We analyzed the influence of SNPs localized in the [–70, –20] region from the transcription start site of the gene on TBP / promoter affinity in two groups of genes that are components of the system of human circadian clock. The first group comprises the genes of the circadian oscillator core (11 genes); the second, the genes of the nearest regulatory environment of the circadian oscillator (21 genes). A group for comparison included genes with another function (31 genes). The SNP_TATA_Comparator web service was used for prediction of the effect of SNPs in the regions of positioning of RNA polymerase II on the dissociation constant for TBP / promoter. It was shown that the number of SNP markers reducing the TBP / promoter affinity in the first group of genes significantly lower than the number of SNP markers increasing affinity (α < 10–3). The reverse was true of the comparison group: SNP markers reduced TBP / promoter affinity to a significantly greater extent than the SNP marker increased affinity (α < 10–6). This property may be a characteristic feature of genes  of the circadian oscillator. These predictions are important for identification of candidate SNP markers of various pathologies associated with the dysfunction of circadian clock genes for further testing them in experimental and clinical studies, as well as for verification of mathematical models of the circadian oscillator.

1. 1 000 Genomes Project Consortium; Abecasis G.R., Auton A., Brooks L. D., DePristo M.A., Durbin R.M., Handsaker R.E., Kang H.M., Marth G.T., McVean G.A. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491:56-65. DOI 10.1038/nature11632

2. Abba M.C., Sun H., Hawkins K.A., Drake J.A., Hu Y., Nunez M.I., Gaddis S., Shi T., Horvath S., Sahin A., Aldaz C.M. Breast cancer molecular signatures as determined by SAGE: correlation with lymph node status. Mol. Cancer Res. 2007;5(9):881-890.

3. Brown S.A., Kowalska E., Dallmann R. (Re)inventing the circadian feedback loop. Dev. Cell. 2012;22(3):477-87. DOI 10.1016/j.devcel.2012.02.007

4. Bryant C.D., Parker C.C., Zhou L., Olker C., Chandrasekaran R.Y., Wager T.T., Bolivar V.J., Loudon A.S., Vitaterna M.H., Turek F . W., Palmer A.A. Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. Neuropsychopharmacology. 2012;37(4): 1026-1035. DOI 10.1038/npp.2011.287

5. Burgueno A.L., Gianotti T.F., Mansilla N.G., Pirola C.J., Sookoian S. Cardiovascular disease is associated with high-fat-diet-induced liver damage and up-regulation of the hepatic expression of hypoxiainducible factor 1α in a rat model. Clin. Sci. (Lond). 2013;124(1): 53-63. DOI 10.1042/CS20120151

6. Cao Q., Gery S., Dashti A., Yin D., Zhou Y., Gu J., Koeffler H.P. A role for the clock gene per1 in prostate cancer. Cancer Res. 2009;69(19):7619-7625. DOI 10.1158/0008-5472.CAN-08-4199

7. Chen L., Yang G. PPARs integrate the mammalian clock and energy metabolism. PPAR Res. 2014;2014:653017. DOI 10.1155/2014/653017

8. Climent J., Perez-Losada J., Quigley D.A., Kim I.J., Delrosario R., Jen K.Y., Bosch A., Lluch A., Mao J.H., Balmain A. Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer. J. Clin. Oncol. 2010;28(23):3770-3778. DOI 10.1200/JCO.2009.27.0215

9. Coma S., Amin D.N., Shimizu A., Lasorella A., Iavarone A., Klagsbrun M. Id2 promotes tumor cell migration and invasion through transcriptional repression of semaphorin 3F. Cancer Res. 2010;70(9): 3823-3832. DOI 10.1158/0008-5472.CAN-09-3048

10. Fang L., Yang Z., Zhou J., Tung J.Y., Hsiao C.D., Wang L., Deng Y., Wang P., Wang J., Lee M.H. Circadian clock gene CRY2 degradation is involved in chemoresistance of colorectal cancer. Mol. Cancer Ther. 2015;14(6):1476-1487. DOI 10.1158/1535-7163.MCT-15-0030

11. Flajolet M., He G., Heiman M., Lin A., Nairn A.C., Greengard P. Regulation of Alzheimer’s disease amyloid-beta formation by casein kinase I. Proc. Natl Acad. Sci. USA. 2007;104:4159-4164.

12. Frankish A., Uszczynska B., Ritchie G.R., Gonzalez J.M., Pervouchine D., Petryszak R., Mudge J., Fonseca N., Brazma A., Guigo R., Harrow J. Comparison of GENCODE and RefSeq gene annotation and the impact of reference geneset on variant effect prediction. BMC Genomics. 2015;16(Suppl.8):S2. DOI 10.1186/1471-2164-16-S8-S2

13. Gao R., Ma Z., Hu Y., Chen J., Shetty S., Fu J. Sirt1 restrains lung inflammasome activation in a murine model of sepsis. Am. J. Physiol. Lung Cell Mol. Physiol. 2015;308(8):L847-L853. DOI 10.1152/ajplung.00274.2014

14. Gery S., Komatsu N., Baldjyan L., Yu A., Koo D., Koeffler H.P. The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol. Cell. 2006;22(3):375-382.

15. Hamzaoui A., Maalmi H., Berraies A., Abid H., Ammar J., Hamzaoui K. Transcriptional characteristics of CD4 T cells in young asthmatic children: RORC and FOXP3 axis. J. Inflamm. Res. 2011a;4:139-146.

16. Hamzaoui K., Borhani Haghighi A., Ghorbel I.B., Houman H. RORC and Foxp3 axis in cerebrospinal fluid of patients with neuro-Behçet’s disease. J. Neuroimmunol. 2011b;233(1/2):249-253. DOI 10.1016/j.jneuroim.2011.01.012

17. Hasan S., van der Veen D.R., Winsky-Sommerer R., Dijk D.J., Archer S.N. Altered sleep and behavioral activity phenotypes in PER3-deficient mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011;301(6):R1821-R1830. DOI 10.1152/ajpregu.00260.2011

18. Hirano A., Yumimoto K., Tsunematsu R., Matsumoto M., Oyama M., Kozuka-Hata H., Nakagawa T., Lanjakornsiripan D., Nakayama K. I., Fukada Y. FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes. Cell. 2013;152(5):1106-1118. DOI 10.1016/j.cell.2013.01.054

19. Howroyd P., Swanson C., Dunn C., Cattley R.C., Corton J.C. Decreased longevity and enhancement of age-dependent lesions in mice lacking the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Toxicol. Pathol. 2004;32(5):591- 599. DOI 10.1080/01926230490515283

20. Jilg A., Lesny S., Peruzki N., Schwegler H., Selbach O., Dehghani F ., Stehle J.H. Temporal dynamics of mouse hippocampal clock gene expression support memory processing. Hippocampus. 2010;20(3): 377-388. DOI 10.1002/hipo.20637

21. Kasowski M., Grubert F., Heffelfinger C., Hariharan M., Asabere A., Waszak S.M., Habegger L., Rozowsky J., Shi M., Urban A.E., Hong M.Y., Karczewski K.J., Huber W., Weissman S.M., Gerstein M.B., Korbel J.O., Snyder M. Variation in transcription factor binding among humans. Science. 2010;328(5975):232-235. DOI 10.1126/science.1183621

22. Kettner N.M., Katchy C.A., Fu L. Circadian gene variants in cancer. Ann. Med. 2014;46(4):208-220. DOI 10.3109/07853890.2014.914808

23. Kim J.K., Forger D.B. A mechanism for robust circadian timekeeping via stoichiometric balance. Mol. Syst. Biol. 2012;8:630. DOI 10.1038/msb.2012.62

24. Ko C.H., Takahashi J.S. Molecular components of the mammalian circadian clock. Hum. Mol. Genet. 2006;15(Spec No 2):R271-277.

25. Korge S., Grudziecki A., Kramer A. Highly efficient genome editing via CRISPR/Cas9 to create clock gene knockout cells. J. Biol. Rhythms. 2015;30(5):389-395. DOI 10.1177/0748730415597519

26. Lin J.C., Lin C.Y., Tarn W.Y., Li F.Y. Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events. RNA. 2014b;20(10):1621-1631. DOI 10.1261/rna.045583.114

27. Lin J.C., Tarn W.Y., Hsieh W.K. Emerging role for RNA binding motif protein 4 in the development of brown adipocytes. Biochim. Biophys. Acta. 2014a;1843(4):769-779. DOI 10.1016/j.bbamcr.2013.12.018

28. Luo Y., Wang F., Chen L.A., Chen X.W., Chen Z.J., Liu P.F., Li F.F., Li C.Y., Liang W. Deregulated expression of cry1 and cry2 in human gliomas. Asian Pac. J. Cancer Prev. 2012;13(11):5725-5728.

29. Mehraj V., Textoris J., Capo C., Raoult D., Leone M., Mege J.L. Overexpression of the Per2 gene in male patients with acute Q fever. J. Infect. Dis. 2012;206(11);1768-1770. DOI 10.1093/infdis/jis600

30. Miyazaki K., Wakabayashi M., Hara Y., Ishida N. Tumor growth suppression in vivo by overexpression of the circadian component, PER2. Genes Cells. 2010;15(4):351-358. DOI 10.1111/j.1365-2443.2010.01384.x

31. Mogno I., Vallania F., Mitra R., Cohen B. TATA is a modular component of synthetic promoters. Genome Res. 2010;20(10):1391-1397. DOI 10.1101/gr.106732.110

32. Nencioni A., da Silva R.F., Fraga-Silva R.A., Steffens S., Fabre M., Bauer I., Caffa I., Magnone M., Sociali G., Quercioli A., Pelli G., Lenglet S., Galan K., Burger F., Vazquez Calvo S., Bertolotto M., Bruzzone S., Ballestrero A., Patrone F., Dallegri F., Santos R.A., Stergiopulos N., Mach F., Vuilleumier N., Montecucco F. Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice. Thromb. Haemost. 2014;111(2):308-322. DOI 10.1160/TH13-07-0531

33. Oishi K., Ohkura N., Amagai N., Ishida N. Involvement of circadian clock gene Clock in diabetes-induced circadian augmentation of plasminogen activator inhibitor-1 (PAI-1) expression in the mouse heart. FEBS Lett. 2005;579(17):3555-3559.

34. Oshima T., Takenoshita S., Akaike M., Kunisaki C., Fujii S., Nozaki A., Numata K., Shiozawa M., Rino Y., Tanaka K., Masuda M., Imada T. Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer. Oncol. Rep. 2011;25(5):1439-1446. DOI 10.3892/or.2011.1207

35. Pereira D.S., van der Veen D.R., Gonçalves B.S., Tufik S., von Schantz M., Archer S.N., Pedrazzoli M. The effect of different photoperiods in circadian rhythms of per3 knockout mice. Biomed. Res. Int. 2014;2014:170795. DOI 10.1155/2014/170795

36. Podkolodnaya O.A. Molecular and genetic aspects of interactions of the circadian clock and the energy producing substrate metabolism in mammals. Genetika = Genetics (Moscow). 2014;50(2):125-137.

37. Podkolodnaya O.A. Podkolodnaya N.N. Podkolodnyy N.L. The mammalian circadian clock: gene regulatory network and computer analysis. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2014;18(4/2):928-938.

38. Ponomarenko M., Rasskazov D., Arkova O., Ponomarenko P., Suslov V., Savinkova L., Kolchanov N. How to use SNP_TATA_Comparator to find a significant change in gene expression caused by the regulatory SNP of this gene’s promoter via a change in affinity of the TATA-binding protein for this promoter. Biomed. Res. Int. 2015;2015:359835 (in press).

39. Rasskazov D.A., Gunbin K.V., Ponomarenko P.M., Vishnevsky O.V., Ponomarenko M.P., Afonnikov D.A. SNP_TATA_Comparator: Web-service for comparison of SNPs within gene promotеrs associated with human diseases using the equilibrium equation of the TBP/ TATA complex. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2013;17(4/1):599-606.

40. Reppert M., Weaver D.R. Molecular analysis of mammalian circadian rhythms. Annu. Rev. Physiol. 2001;63:647-676.

41. Rodriguez N., Yang J., Hasselblatt K., Liu S., Zhou Y., Rauh-Hain J. A., Ng S.K., Choi P.W., Fong W.P., Agar N.Y., Welch W.R., Berkowitz R.S., Ng S.W. Casein kinase I epsilon interacts with mitochondrial proteins for the growth and survival of human ovarian cancer cells. EMBO Mol. Med. 2012;4:952-963. DOI 10.1002/emmm.201101094

42. Sahar S., Sassone-Corsi P. Regulation of metabolism: the circadian clock dictates the time. Trends Endocrinol. Metab. 2012;23(1):1-8. DOI 10.1016/j.tem.2011.10.005

43. Sato F., Kawamura H., Wu Y., Sato H., Jin D., Bhawal U.K., Kawamoto T., Fujimoto K., Noshiro M., Seino H., Morohashi S., Kato Y., Kijima H. The basic helix-loop-helix transcription factor DEC2 inhibits TGF-β-induced tumor progression in human pancreatic cancer BxPC-3 cells. Int. J. Mol. Med. 2012;30(3):495-501. DOI 10.3892/ijmm.2012.1037

44. Savinkova L.K., Drachkova I.A., Arshinova T.V., Ponomarenko P.M., Ponomarenko M.P., Kolchanov N.A. An experimental verification of the predicted effects of promoter TATA-box polymorphisms associated with human diseases on interactions between the TATA boxes and TATA-binding protein. PLoS One. 2013; 8(2):e54626. DOI 10.1371/journal.pone.0054626

45. Sawicka-Gutaj N., Waligorska-Stachura J., Andrusiewicz M., Biczysko M., Sowinski J., Skrobisz J., Ruchala M. Nicotinamide phosphorybosiltransferase overexpression in thyroid malignancies and its correlation with tumor stage and with survivin/survivin DEx3 expression. Tumour Biol. 2015;36(10):7859-7863. DOI 10.1007/s13277-015-3506-z

46. Shi Y., Cao J., Gao J., Zheng L., Goodwin A., An C.H., Patel A., Lee J. S., Duncan S.R., Kaminski N., Pandit K.V., Rosas I.O., Choi A. M., Morse D. Retinoic acid- related orphan receptor-α is induced in the setting of DNA damage and promotes pulmonary emphysema. Am. J. Respir. Crit. Care Med. 2012;186(5):412-419. DOI 10.1164/rccm.201111-2023OC

47. Toyoshima M., Howie H.L., Imakura M., Walsh R.M., Annis J.E., Chang A.N., Frazier J., Chau B.N., Loboda A., Linsley P.S., Cleary M.A., Park J.R., Grandori C. Functional genomics identifies therapeutic targets for MYC-driven cancer. Proc. Natl Acad. Sci. USA. 2012;109(24):9545-9550. DOI 10.1073/pnas.1121119109

48. Wang Q., Maillard M., Schibler U., Burnier M., Gachon F. Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2010; 299(4):R1013-R1019. DOI 10.1152/ajpregu.00241.2010

49. Wang T., Yang P., Zhan Y., Xia L., Hua Z., Zhang J. Deletion of circadian gene Per1 alleviates acute ethanol-induced hepatotoxicity in mice. Toxicology. 2013;314(2/3):193-201. DOI 10.1016/j.tox.2013.09.009

50. Watanabe S., Ageta-Ishihara N., Nagatsu S., Takao K., Komine O., Endo F., Miyakawa T., Misawa H., Takahashi R., Kinoshita M., Yamanaka K. SIRT1 overexpression ameliorates a mouse model of SOD1-linked amyotrophic lateral sclerosis via HSF1/HSP70i chaperone system. Mol. Brain. 2014;7:62. DOI 10.1186/s13041-014-0062-1

51. Wilmet J.P., Tastet C., Desruelles E., Ziental-Gelus N., Blanckaert V., Hondermarck H., Le Bourhis X. Proteome changes induced by overexpression of the p75 neurotrophin receptor (p75NTR) in breast cancer cells. Int. J. Dev. Biol. 2011;55(7-9):801-809. DOI 10.1387/ijdb.113345jw

52. Wong V.C., Ko J.M., Qi R.Z., Li P.J., Wang L.D., Li J.L., Chan Y.P., Chan K.W., Stanbridge E.J., Lung M.L. Abrogated expression of DEC1 during oesophageal squamous cell carcinoma progression is age- and family history-related and significantly associated with lymph node metastasis. Br. J. Cancer. 2011;104(5):841-849. DOI 10.1038/bjc.2011.25

53. Yamasaki N., Miyazaki K., Nagamachi A., Koller R., Oda H., Miyazaki M., Sasaki T., Honda Z.I., Wolff L., Inaba T., Honda H. Identification of Zfp521/ZNF521 as a cooperative gene for E2A-HLF to develop acute B-lineage leukemia. Oncogene. 2010;29(13):1963-1975. DOI 10.1038/onc.2009.475

54. Yu S., Matsusue K., Kashireddy P., Cao W.Q., Yeldandi V., Yeldandi A. V., Rao M.S., Gonzalez F.J., Reddy J.K. Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (PPARgamma1) overexpression. J. Biol. Chem. 2003;278(1):498-505. DOI 10.1074/jbc.M210062200

55. Yumimoto K., Akiyoshi S., Ueo H., Sagara Y., Onoyama I., Ueo H., Ohno S., Mori M., Mimori K., Nakayama K.I. F-box protein FBXW7 inhibits cancer metastasis in a non- cell-autonomous manner. J. Clin. Invest. 2015;125(2):621-635. DOI 10.1172/JCI78782

56. Zerbino D.R., Wilder S.P., Johnson N., Juettemann T., Flicek P.R. The Ensembl regulatory build. Genome Biol. 2015;16:56. DOI 10.1186/s13059-015-0621-5

57. Zhao H., Zeng Z.L., Yang J., Jin Y., Qiu M.Z., Hu X.Y., Han J., Liu K.Y., Liao J.W., Xu R.H., Zou Q.F. Prognostic relevance of Period1 (Per1) and Period2 (Per2) expression in human gastric cancer. Int. J. Clin. Exp. Pathol. 2014;7(2):619-630.