Functional implications of the CLOCK3111T/C single-nucleotide polymorphism

Angela Ozburn, Kush Purohit, Puja K. Parekh, Gabrielle N. Kaplan, Edgardo Falcon, Shibani Mukherjee, Hannah M. Cates, Colleen A. McClung

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Circadian rhythm disruptions are prominently associated with bipolar disorder (BD). Circadian rhythms are regulated by the molecular clock, a family of proteins that function together in a transcriptional-translational feedback loop. The CLOCK protein is a key transcription factor of this feedback loop, and previous studies have found that manipulations of the Clock gene are sufficient to produce manic-like behavior in mice (1). The CLOCK 3111T/C single-nucleotide polymorphism (SNP; rs1801260) is a genetic variation of the human CLOCK gene that is significantly associated with increased frequency of manic episodes in BD patients (2). The 3111T/C SNP is located in the 3'-untranslated region of the CLOCK gene. In this study, we sought to examine the functional implications of the human CLOCK 3111T/C SNP by transfecting a mammalian cell line (mouse embryonic fibroblasts isolated from Clock-/- knockout mice) with pcDNA plasmids containing the human CLOCK gene with either the T or C SNP at position 3111. We then measured circadian gene expression over a 24-h time period. We found that the CLOCK3111C SNP resulted in higher mRNA levels than the CLOCK 3111T SNP. Furthermore, we found that Per2, a transcriptional target of CLOCK, was also more highly expressed with CLOCK 3111C expression, indicating that the 3'-UTR SNP affects the expression, function, and stability of CLOCK mRNA.

Original languageEnglish (US)
Article number67
JournalFrontiers in Psychiatry
Volume7
Issue numberAPR
DOIs
StatePublished - Apr 21 2016

Fingerprint

Single Nucleotide Polymorphism
3' Untranslated Regions
Circadian Rhythm
Bipolar Disorder
Genes
CLOCK Proteins
RNA Stability
Knockout Mice
Plasmids
Transcription Factors
Fibroblasts
Gene Expression
Cell Line
Messenger RNA
Proteins

Keywords

  • Bipolar disorder
  • Cell culture
  • Circadian
  • Clock
  • Gene expression
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Ozburn, A., Purohit, K., Parekh, P. K., Kaplan, G. N., Falcon, E., Mukherjee, S., ... McClung, C. A. (2016). Functional implications of the CLOCK3111T/C single-nucleotide polymorphism. Frontiers in Psychiatry, 7(APR), [67]. https://doi.org/10.3389/fpsyt.2016.00067

Functional implications of the CLOCK3111T/C single-nucleotide polymorphism. / Ozburn, Angela; Purohit, Kush; Parekh, Puja K.; Kaplan, Gabrielle N.; Falcon, Edgardo; Mukherjee, Shibani; Cates, Hannah M.; McClung, Colleen A.

In: Frontiers in Psychiatry, Vol. 7, No. APR, 67, 21.04.2016.

Research output: Contribution to journalArticle

Ozburn, A, Purohit, K, Parekh, PK, Kaplan, GN, Falcon, E, Mukherjee, S, Cates, HM & McClung, CA 2016, 'Functional implications of the CLOCK3111T/C single-nucleotide polymorphism', Frontiers in Psychiatry, vol. 7, no. APR, 67. https://doi.org/10.3389/fpsyt.2016.00067
Ozburn, Angela ; Purohit, Kush ; Parekh, Puja K. ; Kaplan, Gabrielle N. ; Falcon, Edgardo ; Mukherjee, Shibani ; Cates, Hannah M. ; McClung, Colleen A. / Functional implications of the CLOCK3111T/C single-nucleotide polymorphism. In: Frontiers in Psychiatry. 2016 ; Vol. 7, No. APR.
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