{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T06:41:00Z","timestamp":1776148860526,"version":"3.50.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autophagy, a fundamental cellular process, is indispensable for maintaining cellular homeostasis through the regulated degradation and recycling of intracellular components, including damaged organelles and invading pathogens. ATG16L2 is a key autophagy gene essential for autophagosome formation and maturation. Unraveling the intricate transcriptional regulation of such autophagy-related genes is paramount for optimizing livestock germplasm and enhancing breeding programs. This study aimed to comprehensively elucidate the transcriptional regulation of the goat ATG16L2 gene. Tissue-specific qPCR analysis revealed the highest ATG16L2 mRNA expression in the goat spleen among key tissues examined (liver, spleen, lung, kidney, fat, rumen, and small intestine). Subsequently, to characterize the ATG16L2 promoter, we cloned a 1,304\u2009bp upstream sequence (from \u22121,080 to +224 relative to the transcription start site, TSS). Truncated promoter constructs derived from this fragment were evaluated via dual-luciferase reporter assays to identify the core promoter region. To investigate the transcriptional regulation of goat ATG16L2, small interfering RNAs (siRNA) were used to target specific transcription factors. Dual-luciferase reporter assays demonstrated that deleting the identified SMAD5 binding site significantly diminished promoter activity. This was further supported by siRNA-mediated knockdown of SMAD5, which led to reduced luciferase activity in transfected goat primary fibroblasts. In conclusion, we identified the core promoter region of the goat ATG16L2 gene that maintains basal transcription and demonstrated the role of SMAD5 in its transcriptional regulation, laying the foundation for future studies on the function of goat ATG16L2.<\/jats:p>","DOI":"10.1093\/jas\/skag089","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T23:51:31Z","timestamp":1774309891000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>SMAD5<\/i>\n                    regulates Hainan Black Goat\n                    <i>ATG16L2<\/i>\n                    gene transcription in primary goat fibroblasts"],"prefix":"10.1093","volume":"104","author":[{"given":"Huan","family":"Wang","sequence":"first","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hejie","family":"Qian","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Meng","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihua","family":"Niu","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Churiga","family":"Man","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Gao","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoling","family":"Chen","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Du","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[{"name":"Hainan University Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, , Haikou 570228,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"2026041401420218000_skag089-B1","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.2147\/IDR.S471204","article-title":"The roles of endocytosis and autophagy at the cellular level during influenza virus infection: a mini-review","volume":"17","author":"Sulpiana, Amalia","year":"2024","journal-title":"Infect Drug Resist"},{"key":"2026041401420218000_skag089-B2","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.fob.2014.03.008","article-title":"The role of autophagy in the intracellular survival of Campylobacter concisus","volume":"4","author":"Burgos-Portugal","year":"2014","journal-title":"FEBS Open Bio"},{"key":"2026041401420218000_skag089-B3","doi-asserted-by":"publisher","first-page":"4112","DOI":"10.1111\/febs.16298","article-title":"Innate immunity and inflammophagy: balancing the defence and immune homeostasis","volume":"289","author":"Chauhan","year":"2022","journal-title":"Febs J"},{"key":"2026041401420218000_skag089-B4","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.3390\/genes13091539","article-title":"Whole-genome sequencing reveals the genomic characteristics and selection signatures of Hainan black goat","volume":"13","author":"Chen","year":"2022","journal-title":"Genes (Basel)"},{"key":"2026041401420218000_skag089-B5","doi-asserted-by":"publisher","first-page":"19979","DOI":"10.1038\/s41598-025-86048-1","article-title":"EIF4A3 enhances the viability, invasion and osteogenic differentiation of BMSCs via the USP53\/SMAD5 pathway","volume":"15","author":"Cheng","year":"2025","journal-title":"Sci Rep"},{"key":"2026041401420218000_skag089-B6","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1080\/15548627.2023.2173900","article-title":"Phosphorylation of EIF2S1 (eukaryotic translation initiation factor 2 subunit alpha) is indispensable for nuclear translocation of TFEB and TFE3 during ER stress","volume":"19","author":"Dang","year":"2023","journal-title":"Autophagy"},{"key":"2026041401420218000_skag089-B7","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.immuni.2021.01.018","article-title":"Autophagy in inflammation, infection, and immunometabolism","volume":"54","author":"Deretic","year":"2021","journal-title":"Immunity"},{"key":"2026041401420218000_skag089-B8","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.15252\/embj.201796697","article-title":"Molecular definitions of autophagy and related processes","volume":"36","author":"Galluzzi","year":"2017","journal-title":"Embo J"},{"key":"2026041401420218000_skag089-B9","doi-asserted-by":"publisher","first-page":"jcs249227","DOI":"10.1242\/jcs.249227","article-title":"The multifaceted functions of ATG16L1 in autophagy and related processes","volume":"133","author":"Gammoh","year":"2020","journal-title":"J Cell Sci"},{"key":"2026041401420218000_skag089-B10","doi-asserted-by":"publisher","first-page":"e309","DOI":"10.1002\/mco2.309","article-title":"TRAF6 regulates autophagy and apoptosis of melanoma cells through c-Jun\/ATG16L2 signaling pathway","volume":"4","author":"Guo","year":"2023","journal-title":"MedComm (2020)."},{"key":"2026041401420218000_skag089-B11","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41580-018-0028-8","article-title":"Eukaryotic core promoters and the functional basis of transcription initiation","volume":"19","author":"Haberle","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026041401420218000_skag089-B12","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.molcel.2017.06.017","article-title":"The unfolded protein response and cell fate control","volume":"69","author":"Hetz","year":"2018","journal-title":"Mol Cell"},{"key":"2026041401420218000_skag089-B13","doi-asserted-by":"publisher","first-page":"3938","DOI":"10.4161\/cc.10.22.18107","article-title":"Phospho-\u0394Np63\u03b1\/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure","volume":"10","author":"Huang","year":"2011","journal-title":"Cell Cycle (Georgetown Tex.)"},{"key":"2026041401420218000_skag089-B14","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.4161\/auto.7.12.18025","article-title":"Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12\u20135-16L2 complex","volume":"7","author":"Ishibashi","year":"2011","journal-title":"Autophagy"},{"key":"2026041401420218000_skag089-B15","doi-asserted-by":"publisher","first-page":"768935","DOI":"10.3389\/fimmu.2021.768935","article-title":"Editorial: the autophagy pathway: bacterial pathogen immunity and evasion","volume":"12","author":"Jagannath","year":"2021","journal-title":"Front Immunol"},{"key":"2026041401420218000_skag089-B16","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neuroscience.2019.06.008","article-title":"LRG1 promotes apoptosis and autophagy through the TGF\u03b2-smad1\/5 signaling pathway to exacerbate ischemia\/reperfusion injury","volume":"413","author":"Jin","year":"2019","journal-title":"Neuroscience"},{"key":"2026041401420218000_skag089-B17","doi-asserted-by":"publisher","first-page":"5779","DOI":"10.1038\/ncomms6779","article-title":"Autophagy enhances NF\u03baB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity","volume":"6","author":"Kanayama","year":"2015","journal-title":"Nat Commun"},{"key":"2026041401420218000_skag089-B18","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/08830185.2023.2296488","article-title":"HCMV miR-UL70-3p downregulates the rapamycin-induced autophagy by targeting the autophagy-related protein 9A (ATG9A)","volume":"43","author":"Khalko","year":"2024","journal-title":"Int Rev Immunol"},{"key":"2026041401420218000_skag089-B19","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.4049\/jimmunol.1800419","article-title":"Distinct tissue-specific roles for the disease-associated autophagy genes ATG16L2 and ATG16L1","volume":"203","author":"Khor","year":"2019","journal-title":"J Immunol"},{"key":"2026041401420218000_skag089-B20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"2026041401420218000_skag089-B21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological functions of autophagy genes: a disease perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"2026041401420218000_skag089-B22","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1172\/jci64498","article-title":"Loss of acinar cell IKK\u03b1 triggers spontaneous pancreatitis in mice","volume":"123","author":"Li","year":"2013","journal-title":"J Clin Invest"},{"key":"2026041401420218000_skag089-B23","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.jor.2024.10.047","article-title":"Transcription factor SMAD5 upregulates ALG5 to alleviate osteoporosis development by inducing osteogenic differentiation","volume":"61","author":"Li","year":"2025","journal-title":"J Orthop"},{"key":"2026041401420218000_skag089-B24","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12863-024-01228-8","article-title":"Development and verification of a 10K liquid chip for Hainan black goat based on genotyping by pinpoint sequencing of liquid captured targets","volume":"25","author":"Meng","year":"2024","journal-title":"BMC Genom Data"},{"key":"2026041401420218000_skag089-B25","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"2026041401420218000_skag089-B26","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1093\/hmg\/ddx026","article-title":"Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci","volume":"26","author":"Molineros","year":"2017","journal-title":"Hum Mol Genet"},{"key":"2026041401420218000_skag089-B27","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/nature07383","article-title":"Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production","volume":"456","author":"Saitoh","year":"2008","journal-title":"Nature"},{"key":"2026041401420218000_skag089-B28","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1080\/15548627.2017.1364822","article-title":"Transcriptional regulation of autophagy and lysosomal function by bromodomain protein BRD4","volume":"13","author":"Sakamaki","year":"2017","journal-title":"Autophagy"},{"key":"2026041401420218000_skag089-B29","doi-asserted-by":"publisher","first-page":"20086","DOI":"10.1038\/s41598-023-46997-x","article-title":"New insights into the genetic predisposition of brucellosis and its effect on the gut and vaginal microbiota in goats","volume":"13","author":"Sallam","year":"2023","journal-title":"Sci Rep"},{"key":"2026041401420218000_skag089-B30","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1177\/1099800421994186","article-title":"Enhancing research through the use of the genotype-tissue expression (GTEx) database","volume":"23","author":"Stanfill","year":"2021","journal-title":"Biol Res Nurs"},{"key":"2026041401420218000_skag089-B31","doi-asserted-by":"publisher","first-page":"10453","DOI":"10.2147\/JIR.S483958","article-title":"Exploring the connections: autophagy, gut microbiota, and inflammatory bowel disease pathogenesis","volume":"17","author":"Subramanian","year":"2024","journal-title":"J Inflamm Res"},{"key":"2026041401420218000_skag089-B32","doi-asserted-by":"publisher","first-page":"1245443","DOI":"10.3389\/fimmu.2023.1245443","article-title":"p38(MAPK)\/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection","volume":"14","author":"Suwandi","year":"2023","journal-title":"Front Immunol"},{"key":"2026041401420218000_skag089-B33","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1080\/15548627.2020.1798064","article-title":"Autophagy in farm animals: current knowledge and future challenges","volume":"17","author":"Tesseraud","year":"2021","journal-title":"Autophagy"},{"key":"2026041401420218000_skag089-B34","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: from stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Science"},{"key":"2026041401420218000_skag089-B35","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1002\/eji.202149764","article-title":"ATG16L2 inhibits NLRP3 inflammasome activation through promoting ATG5-12-16L1 complex assembly and autophagy","volume":"52","author":"Wang","year":"2022","journal-title":"Eur J Immunol"},{"key":"2026041401420218000_skag089-B36","doi-asserted-by":"publisher","first-page":"9590","DOI":"10.18632\/aging.205037","article-title":"YY1 is regulated by ALKBH5-mediated m6A modification and promotes autophagy and cancer progression through targeting ATG4B","volume":"15","author":"Wang","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"2026041401420218000_skag089-B37","doi-asserted-by":"publisher","first-page":"e2451078","DOI":"10.1002\/eji.202451078","article-title":"Atg16l2 augments Nlrc4 inflammasome activation by facilitating NAIPs-NLRC4 association","volume":"54","author":"Wen","year":"2024","journal-title":"Eur J Immunol"},{"key":"2026041401420218000_skag089-B38","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.1080\/15548627.2023.2200625","article-title":"NR3C1\/glucocorticoid receptor activation promotes pancreatic \u03b2-cell autophagy overload in response to glucolipotoxicity","volume":"19","author":"Wu","year":"2023","journal-title":"Autophagy"},{"key":"2026041401420218000_skag089-B39","doi-asserted-by":"publisher","first-page":"863","DOI":"10.3390\/pathogens11080863","article-title":"LC3-associated phagocytosis in bacterial infection","volume":"11","author":"Yuan","year":"2022","journal-title":"Pathogens"},{"key":"2026041401420218000_skag089-B40","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1186\/s13018-024-04933-3","article-title":"The SPI1\/SMAD5 cascade in the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells: a mechanism study","volume":"19","author":"Zhang","year":"2024","journal-title":"J Orthop Surg Res"},{"key":"2026041401420218000_skag089-B41","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.chom.2008.10.003","article-title":"Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens","volume":"4","author":"Zhao","year":"2008","journal-title":"Cell Host Microbe"},{"key":"2026041401420218000_skag089-B42","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1186\/s13018-023-04133-5","article-title":"Circ_0001825 promotes osteogenic differentiation in human-derived mesenchymal stem cells via miR-1270\/SMAD5 axis","volume":"18","author":"Zheng","year":"2023","journal-title":"J Orthop Surg Res"},{"key":"2026041401420218000_skag089-B43","doi-asserted-by":"publisher","first-page":"2382766","DOI":"10.1080\/19490976.2024.2382766","article-title":"AUF1-mediated inhibition of autophagic lysosomal degradation contributes to CagA stability and Helicobacter pylori-induced inflammation","volume":"16","author":"Zheng","year":"2024","journal-title":"Gut Microbes"},{"key":"2026041401420218000_skag089-B44","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1016\/j.scib.2024.01.015","article-title":"LSD1 promotes the FSH responsive follicle formation by regulating autophagy and repressing Wt1 in the granulosa cells","volume":"69","author":"Zhu","year":"2024","journal-title":"Sci Bull (Beijing)"}],"container-title":["Journal of Animal Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jas\/advance-article-pdf\/doi\/10.1093\/jas\/skag089\/67485457\/skag089.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jas\/article-pdf\/doi\/10.1093\/jas\/skag089\/67485457\/skag089.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jas\/article-pdf\/doi\/10.1093\/jas\/skag089\/67485457\/skag089.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:42:09Z","timestamp":1776145329000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jas\/article\/doi\/10.1093\/jas\/skag089\/8537934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":44,"URL":"https:\/\/doi.org\/10.1093\/jas\/skag089","relation":{},"ISSN":["0021-8812","1525-3163"],"issn-type":[{"value":"0021-8812","type":"print"},{"value":"1525-3163","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"skag089"}}