{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:11:46Z","timestamp":1789992706023,"version":"4.0.1"},"reference-count":104,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32472867"],"award-info":[{"award-number":["32472867"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32472867"],"award-info":[{"award-number":["32472867"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Non-coding negative regulation is an important but incompletely resolved component of gene-expression control in livestock. We conducted a narrative review using PubMed, Web of Science Core Collection, and Scopus, prioritizing primary studies in pigs, cattle, sheep, goats, and poultry and using model-organism studies only for directly relevant mechanistic or methodological evidence. We distinguish sequence-defined silencers, context-dependent enhancer-silencer elements, functional microRNA-binding sites, long non-coding RNA-associated regulation, and candidate repressive chromatin regions, and evaluate representative livestock studies using a four-tier framework comprising candidate annotation, molecular functional evidence, endogenous causal evidence, and animal-level validation. Current evidence is strongest for a small number of loci, whereas many of the livestock candidates reviewed here are supported primarily by association, chromatin state, or in vitro assays. We further assess how multi-omics data can prioritize candidates and assign target genes, while emphasizing that reporter activity, repressive chromatin marks, and population association do not establish endogenous causality. Progress will depend on locus-specific perturbation, rescue experiments, relevant animal phenotyping, and inheritance testing. This evidence-centered framework provides a focused basis for interpreting negative regulatory variation in livestock and identifying robust targets for future genetic improvement.<\/jats:p>","DOI":"10.3390\/ani16182956","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:05:53Z","timestamp":1789988753000},"page":"2956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Coding Negative Regulatory Features in Livestock Genomes: Functional Annotation and Causal Validation"],"prefix":"10.3390","volume":"16","author":[{"given":"Lingzehui","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijun","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Meat Sheep Genetic Breeding, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China"},{"name":"Key Laboratory of Sheep Genetic Breeding and Reproduction of Inner Mongolia Autonomous Region, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Meat Sheep Genetic Breeding, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China"},{"name":"Key Laboratory of Sheep Genetic Breeding and Reproduction of Inner Mongolia Autonomous Region, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzheng","family":"Shang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Meat Sheep Genetic Breeding, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China"},{"name":"Key Laboratory of Sheep Genetic Breeding and Reproduction of Inner Mongolia Autonomous Region, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/s41467-017-02809-1","article-title":"Sheep genome functional annotation reveals proximal regulatory elements contributed to the evolution of modern breeds","volume":"9","author":"Sanchez","year":"2018","journal-title":"Nat. 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