{"doi":"10.1016/j.jid.2024.05.010","title":"Analysis of Circadian Clock Gene Expression in Epidermal Human Skin Indicates that Body Location Impacts Rhythm Amplitude","abstract":"Circadian rhythms allow cells, tissues, and whole organisms to adapt to and anticipate changes to environmental conditions and maximize biological fitness. Most mammalian tissues exhibit circadian rhythmicity, including the skin, where a variety of processes ranging from wound healing to immune defense and responses to external stress vary over the course of 24 hr (Duan et al., 2021Duan J. Greenberg E.N. Karri S.S. Andersen B. The circadian clock and diseases of the skin.FEBS Lett. 2021; 595: 2413-2436Crossref PubMed Scopus (26) Google Scholar; Lubov et al., 2021Lubov J.E. Cvammen W. Kemp M.G. The Impact of the Circadian Clock on Skin Physiology and Cancer Development.Int J Mol Sci. 2021; 22Crossref PubMed Scopus (21) Google Scholar). At the molecular level, the circadian clock is governed by a transcription-translation feedback system in which a transcription factor complex (CLOCK-BMAL1) binds to the promoters of many clock-controlled genes (CCGs) to regulate transcription, including that of cryptochrome (CRY) and period (PER), which feedback to inhibit CLOCK-BMAL1 function (Takahashi, 2017Takahashi J.S. Transcriptional architecture of the mammalian circadian clock.Nature reviews.Genetics. 2017; 18: 164-179Crossref PubMed Scopus (0) Google Scholar). Most analyses of circadian gene expression are derived from nocturnal rodent models. Given that humans are diurnal and are exposed to different environmental conditions, it is important to extend such work to human skin. Indeed, two studies with human subjects were conducted in recent years (Del Olmo et al., 2022Del Olmo M. Spörl F. Korge S. Jürchott K. Felten M. Grudziecki A. et al.Inter-layer and inter-subject variability of diurnal gene expression in human skin.NAR Genom Bioinform. 2022; 4lqac097PubMed Google Scholar; Wu et al., 2018Wu G. Ruben M.D. Schmidt R.E. Francey L.J. Smith D.F. Anafi R.C. et al.Population-level rhythms in human skin with implications for circadian medicine.Proc Natl Acad Sci U S A. 2018; 115: 12313-12318Crossref PubMed Scopus (78) Google Scholar), each with unique characteristics in terms of subject recruitment, biopsy location and frequency, and microarray platform (Fig. 1a). Using a previously outlined bioinformatic approach (Wu et al., 2018Wu G. Ruben M.D. Schmidt R.E. Francey L.J. Smith D.F. Anafi R.C. et al.Population-level rhythms in human skin with implications for circadian medicine.Proc Natl Acad Sci U S A. 2018; 115: 12313-12318Crossref PubMed Scopus (78) Google Scholar), we obtained the two transcriptomic datasets from the Gene Expression Omnibus (GEO) and then plotted the relative expression of core circadian clock genes over the course of the day. As shown in Fig. 1b, clear and similar oscillations were observed for most of the genes, including the times of peak and trough gene expression. However, calculation of the amplitudes of the gene expression oscillations revealed modestly higher amplitudes for most of the genes in the Wu et al. study, including for the CRY and PER transcriptional repressors. Because there were differences in the sex of the subjects in the two studies, which could potentially impact circadian rhythms (Cvammen et al., 2024Cvammen W. Rider S.D. Travers J.B. Kemp M.G. Effects of Age and Sex on the Expression of Core Circadian Clock Genes in Human Skin Epidermis.J Invest Dermatol. 2024; 144: 1172-1175Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar), we then compared clock gene expression in males and females from the Del Olmo et al. study. However, though CLOCK and NR1D1 expression exhibited statistically significantly lower amplitudes in females, the other clock genes showed very similar rhythms (Figs 1d-e). Thus, we conclude that sex does not significantly affect the expression of core circadian clock genes in epidermal skin. Using meta3d (Wu et al., 2016Wu G. Anafi R.C. Hughes M.E. Kornacker K. Hogenesch J.B. MetaCycle: an integrated R package to evaluate periodicity in large scale data.Bioinformati","journal":"Journal of Investigative Dermatology","year":2024,"id":471231,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9404,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":872628,"name":"S. Dean Rider","orcid":"0000-0002-5792-3768","position":1,"is_corresponding":false},{"id":390936,"name":"Michael G. Kemp","orcid":"0000-0001-8203-0745","position":2,"is_corresponding":false},{"id":1111489,"name":"William Cvammen","orcid":"0000-0002-6417-905X","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:05:44.736405Z","pmid":"38885877","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}