{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:07:58Z","timestamp":1778519278130,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"ICMR New Delhi","doi-asserted-by":"publisher","award":["IIRPSG-2024-01-03616"],"award-info":[{"award-number":["IIRPSG-2024-01-03616"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epigenomes"],"abstract":"<jats:p>The ubiquitously transcribed tetratricopeptide repeat Y-linked gene (UTY\/KDM6C), a catalytically impaired histone demethylase encoded on the Y chromosome, has garnered increasing attention for its emerging roles in tumorigenesis and cancer progression. Despite high sequence homology with its X-linked paralog UTX\/KDM6A, UTY exhibits markedly reduced or absent H3K27me3 demethylase activity due to critical amino acid substitutions in its Jumonji C domain. Consequently, UTY primarily functions through non-enzymatic mechanisms, acting as a scaffold in chromatin-remodelling complexes like COMPASS and SWI\/SNF, or mediating protein\u2013protein interactions that regulate transcriptional programs independent of demethylation. This aligns with epigenetic dysregulation in cancers, where imbalances in repressive H3K27me3 and active H3K4me either drive tumour suppressor silencing or oncogene activation. Unlike frequently mutated UTX in cancers such as breast, renal cell carcinoma, and acute myeloid leukaemia, UTY\u2019s contributions in cancer are less defined, constrained by male-specific expression. Emerging evidence suggests UTY as a context-dependent tumour suppressor in AML and squamous-like pancreatic ductal adenocarcinoma. While direct functional validation remains limited in several cancer types, UTY is increasingly implicated as a potential tumour suppressor in haematological malignancies and prostate cancer. Therapeutically targeting UTY\u2019s scaffold functions shows promise for male-specific cancers and merits future investigation.<\/jats:p>","DOI":"10.3390\/epigenomes10020031","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T15:39:32Z","timestamp":1778513972000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["UTY (KDM6C) in Cancer: Epigenetic Regulation, Tumour Suppressor Functions, and Clinical Implications"],"prefix":"10.3390","volume":"10","author":[{"given":"Chitrakshi","family":"Chopra","sequence":"first","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Vijaypur, Jammu 181134, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-7483","authenticated-orcid":false,"given":"Chandra Prakash","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology (Laboratory), Dr. Bhim Rao Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-9188","authenticated-orcid":false,"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Vijaypur, Jammu 181134, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s40164-023-00440-z","article-title":"CUL4B-DDB1-COP1-Mediated UTX Downregulation Promotes Colorectal Cancer Progression","volume":"12","author":"Luo","year":"2023","journal-title":"Exp. 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