Host Genomics Plasticity in Response to Ambient Temperature Change: Transcriptional Regulation Induced by Cold Temperature Perception in the Human BEAS-2B Cell Line

Seyeon      Park; Sohyun      Chun; Danuh      Kim

doi:10.2174/1875692111201010033

Abstract

Pharmacogenomics has long attempted to identify genome-drug interactions and environmental exposures as guideposts for personalized medicine. However, non-drug related environmental factors, too, can interact with the host genome and potentially cause confounding in explaining drug-genome interactions. One such environmental factor that has been bracketed out in the past is the ambient temperature change, and ways in which it can influence genomic plasticity. Indeed, recognition of temperature is an important element of microsensory perception that allows cells to evaluate both their external environment and internal physiological milieu. In this paper, we report the changes in global gene expression three hours after a 30-min cold temperature (10°C) treatment in the human bronchial epithelial cell line BEAS-2B using DNA microarrays. We found 11,276 candidate genes (6,297 with increased, 4,979 with decreased expression) that were differentially expressed after low-temperature treatment of BEAS-2B compared to the untreated control cells (p<0.001). Additionally, up- and down-regulated transcription factor genes were further verified using realtime polymerase chain reaction. We found expression changes in response to cold temperature in transcription factor genes such as ZXDA, ZNF44, ZDHHC13, ZNF423, ZFYVE20, ZNF45, ZC3HAV, ZCCHC5, RUNX1T1, DMRT1, STAT4, EFCAB1 and HSFX1 that can alter the temperature-adaptive responsiveness of the bronchial epithelial cells. In summary, we herein show that a moderately cold temperature induces a genome-wide response in the human bronchial epithelial cell line BEAS-2B, and further discuss its relevance for pharmacogenomics and upstream drug discovery. For example, these observations provide a new crucial putative link between ambient temperature and genomic plasticity that together inform personalized medicine such that future pharmacogenomics biomarker discovery research can better control and account for ever-present dynamic environmental exposures such as ambient temperature. We conclude with the implications of these data in relation to rational drug design for neuropathic and other chronic pain syndromes that are in part moderated by host-ambient temperature interactions.

Keywords: Ambient temperature, BEAS-2B cell line, chronic pain syndrome, environmental confounding and biomarker discovery, genome-temperature interaction, genomics plasticity, personalized medicine, transcription factor gene