{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:25:48Z","timestamp":1784921148158,"version":"3.55.0"},"reference-count":156,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK055704, DK114054 (RAS)"],"award-info":[{"award-number":["DK055704, DK114054 (RAS)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intrauterine growth retardation (IUGR), which induces epigenetic modifications and permanent changes in gene expression, has been associated with the development of type 2 diabetes. Using a rat model of IUGR, we performed ChIP-Seq to identify and map genome-wide histone modifications and gene dysregulation in islets from 2- and 10-week rats. IUGR induced significant changes in the enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in both 2-wk and 10-wk islets, which were correlated with expression changes of multiple genes critical for islet function in IUGR islets. ChIP-Seq analysis showed that IUGR-induced histone mark changes were enriched at critical transcription factor binding motifs, such as C\/EBPs, Ets1, Bcl6, Thrb, Ebf1, Sox9, and Mitf. These transcription factors were also identified as top upstream regulators in our previously published transcriptome study. In addition, our ChIP-seq data revealed more than 1000 potential bivalent genes as identified by enrichment of both H3K4me3 and H3K27me3. The poised state of many potential bivalent genes was altered by IUGR, particularly Acod1, Fgf21, Serpina11, Cdh16, Lrrc27, and Lrrc66, key islet genes. Collectively, our findings suggest alterations of histone modification in key transcription factors and genes that may contribute to long-term gene dysregulation and an abnormal islet phenotype in IUGR rats.<\/jats:p>","DOI":"10.3390\/cells9061435","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T05:11:46Z","timestamp":1591765906000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats"],"prefix":"10.3390","volume":"9","author":[{"given":"Yu-Chin","family":"Lien","sequence":"first","affiliation":[{"name":"Center for Research on Reproduction and Women\u2019s Health, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Division of Neonatology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Zhiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7707-1232","authenticated-orcid":false,"given":"Xueqing Maggie","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Center for Research on Reproduction and Women\u2019s Health, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Division of Neonatology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1464-5491.2003.00871.x","article-title":"Is birth weight related to later glucose and insulin metabolism?\u2014A systematic review","volume":"20","author":"Newsome","year":"2003","journal-title":"Diabet. 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