{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:03:41Z","timestamp":1775624621851,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013314","name":"111 Project","doi-asserted-by":"publisher","award":["D18007"],"award-info":[{"award-number":["D18007"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Alveolar macrophages (AMs) play essential roles in maintaining homeostasis and immunity in the lung. The transcription factor PU.1, encoded by SPI1, is a core regulator in multiple immune cell lineages. However, its binding property and regulatory role in AMs remain unclear. The pig serves as an important livestock species and a valuable biomedical model. Using porcine AMs (PAMs) as a model, we combined gene knockdown experiments with multiomic profiling to elucidate the regulatory role of PU.1 in AMs. By integrating the RNA-seq data before and after SPI1 knockdown, we demonstrate that disruption of PU.1 impairs the expression of numerous immune-related genes, including many crucial for innate immune responses. We further employed CUT&amp;Tag to characterize the genome-wide occupancy of PU.1 and the active histone modification H3K27ac, and found that PU.1 primarily binds active cis-regulatory elements (CREs), including a large proportion of enhancers derived from transposable elements. Moreover, integrative analysis identifies a set of CREs and their associated genes, which are putative direct targets of PU.1. Overall, this study provides novel insights into the regulatory role of PU.1 in AMs and extends our knowledge about this core regulator in the mammalian immune system.<\/jats:p>","DOI":"10.3390\/ani16071116","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:19:32Z","timestamp":1775434772000},"page":"1116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiomic Profiling Reveals the Regulation of Many Immune-Related Genes by PU.1 in Porcine Alveolar Macrophages"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4960-7572","authenticated-orcid":false,"given":"Jiayao","family":"Jiang","sequence":"first","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2141-5139","authenticated-orcid":false,"given":"Yanhua","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyang","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Comparative 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cui","family":"Du","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-3027","authenticated-orcid":false,"given":"Mingan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Joint International Research Laboratory of Important Animal Infectious Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou 225009, China"},{"name":"Interdisciplinary Center for Zoonotic Diseases and Biosafety, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cellimm.2018.01.005","article-title":"Alveolar Macrophages","volume":"330","author":"Joshi","year":"2018","journal-title":"Cell Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.immuni.2022.08.010","article-title":"Biology of lung macrophages in health and disease","volume":"55","author":"Aegerter","year":"2022","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.it.2015.03.005","article-title":"Alveolar macrophages and type I IFN in airway homeostasis and immunity","volume":"36","author":"Divangahi","year":"2015","journal-title":"Trends 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