{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:26:49Z","timestamp":1783114009031,"version":"3.54.6"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"16","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK 075033"],"award-info":[{"award-number":["DK 075033"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Enhancers establish proximity with distant target genes to regulate temporospatial gene expression and specify cell identity. Lim domain binding protein 1 (LDB1) is a conserved and widely expressed protein that functions as an enhancer looping factor. Previous studies in erythroid cells and neuronal cells showed that LDB1 forms protein complexes with different transcription factors to regulate cell-specific gene expression. Here, we show that LDB1 regulates expression of liver genes by occupying enhancer elements and cooperating with hepatic transcription factors HNF4A, FOXA1, TCF7 and GATA4. Using the glucose transporter SLC2A2 gene, encoding GLUT2, as an example, we find that LDB1 regulates gene expression by mediating enhancer\u2013promoter interactions. In vivo, we find that LDB1 deficiency in primary mouse hepatocytes dysregulates metabolic gene expression and changes the enhancer landscape. Conditional deletion of LDB1 in adult mouse liver induces glucose intolerance. However, Ldb1 knockout hepatocytes show improved liver pathology under high-fat diet conditions associated with increased expression of genes related to liver fatty acid metabolic processes. Thus, LDB1 is linked to liver metabolic functions under normal and obesogenic conditions.<\/jats:p>","DOI":"10.1093\/nar\/gkac707","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T17:08:13Z","timestamp":1661533693000},"page":"9195-9211","source":"Crossref","is-referenced-by-count":15,"title":["Enhancer looping protein LDB1 regulates hepatocyte gene expression by cooperating with liver transcription factors"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-7889","authenticated-orcid":false,"given":"Guoyou","family":"Liu","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda , MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0818-1232","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Wess","sequence":"additional","affiliation":[{"name":"Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda , MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6558-747X","authenticated-orcid":false,"given":"Ann","family":"Dean","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"2022090900042524500_B1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature11082","article-title":"Topological domains in mammalian genomes identified by analysis of chromatin interactions","volume":"485","author":"Dixon","year":"2012","journal-title":"Nature"},{"key":"2022090900042524500_B2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature11049","article-title":"Spatial partitioning of the regulatory landscape of the X-inactivation centre","volume":"485","author":"Nora","year":"2012","journal-title":"Nature"},{"key":"2022090900042524500_B3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.cell.2017.09.026","article-title":"Cohesin loss eliminates all loop domains","volume":"171","author":"Rao","year":"2017","journal-title":"Cell"},{"key":"2022090900042524500_B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.molcel.2014.06.015","article-title":"Enhancer function: mechanistic and genome-wide insights come together","volume":"55","author":"Plank","year":"2014","journal-title":"Mol. 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