Next Article in Journal
Sex Chromosomes and Sex Phenotype Contribute to Biased DNA Methylation in Mouse Liver
Next Article in Special Issue
Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity
Previous Article in Journal
Mechanical Adaptations of Epithelial Cells on Various Protruded Convex Geometries
Previous Article in Special Issue
Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress
Open AccessArticle

Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

1
Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA
2
Division of Neonatology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
3
Institute for Biomedical Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1435; https://doi.org/10.3390/cells9061435
Received: 22 April 2020 / Revised: 30 May 2020 / Accepted: 4 June 2020 / Published: 9 June 2020
(This article belongs to the Special Issue Molecular Mechanisms in Metabolic Disease)
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. View Full-Text
Keywords: islets; histone modifications; ChIP-Seq; intrauterine growth restriction; epigenetics; transcription factor binding motif; bivalent gene islets; histone modifications; ChIP-Seq; intrauterine growth restriction; epigenetics; transcription factor binding motif; bivalent gene
Show Figures

Figure 1

MDPI and ACS Style

Lien, Y.-C.; Wang, P.Z.; Lu, X.M.; Simmons, R.A. Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats. Cells 2020, 9, 1435.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop