Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1
J. Clin. Invest. Jun H. Park, et al. 118:2316 doi:10.1172/JCI33655 [
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Figure 7Summary of epigenetic changes at
Pdx1 in IUGR rats during the development of type 2 diabetes.
In pancreatic β-cells (top row), the
Pdx1 proximal promoter is normally found in an unmethylated (open circles) open chromatin state, allowing access to transcription factors such as USF-1 and associated with nucleosomes characterized by acetylated (Ac, octagons) histones H3 and H4 and with H3K4me3 (Me3, hexagons). In IUGR fetal and 2 week islets (second and third rows), histone acetylation is progressively lost through association with a mSin3A-HDAC1-DNMT1 repressor complex, with H3K4me3 disappearing and H3K9me2 (Me2, triangles) appearing after birth. IUGR adult islets (fourth row) are characterized by inactive chromatin with H3K9me2 and extensive DNA methylation (filled circles) locking in the transcriptionally silent state of
Pdx1.
