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Hepatic eEF2K downregulation is associated with altered nucleosome positioning in neonatal IUGR rats
Author(s) -
Fu Qi,
McKnight Robert A.,
Yu Xing,
Callaway Christopher W.,
Lane Robert H.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.456.6
Subject(s) - epigenetics , nucleosome , histone , dna methylation , biology , microbiology and biotechnology , downregulation and upregulation , histone h3 , cpg site , gene , chemistry , genetics , gene expression
Uteroplacental insufficiency (UPI) alters protein synthesis in intrauterine growth restriction (IUGR). Protein synthesis is regulated in part, by eukaryotic elongation factor 2 kinase (eEF2K). eEF2K, a CpG‐rich gene, is down regulated in IUGR rat liver. Our group has shown that UPI alters epigenetic events on genes that have multiple promoters and splice variants. What is not known is how UPI influences epigenetic regulation in CpG island genes. We therefore analyzed the effects of UPI on eEF2K in terms of DNA methylation, histone covalent modifications, and nucleosome positioning around the transcription start in IUGR rat liver. Bisulfite sequencing, ChIP and SssI MTase footprining were performed. The eEF2K promoter had significantly increased DNA methylation, decreased H3acK9, K14, me1K4, me3K4, and me3K36. In addition, the +1 nucleosome accessibility was significantly restricted, together with increased H2A occupancy and decreased RNA polII loading in IUGR relative to the control. In conclusion, UPI induced changes in DNA and histone covalent modifications, nucleosome position and polII loading. We speculate that these changes contribute to eEF2K downregulation.