Research Perspective Volume 3, Issue 5 pp 548—554

Figure 2. Model of epigenetic control at the Hnf4a locus. (A) In young control islets the P2 promoter has low levels of DNA methylation and is associated with open chromatin and high levels of transcription (enrichment in H3Ac and H3K4me3). An active downstream enhancer (enriched in H3Ac and H3K4me1) is essential for high levels of P2 transcription. Accessibility of transcription factors to the P1 promoter is blocked by DNA methylation and H3K9me2. (B) Down-regulation of P2 transcriptional activity in young LP islets results from loss of enhancer activity. The enhancer adopts a closed chromatin configuration with enrichment in H3K9me2 and depletion of active histone marks. (C) Transcriptional silencing along the Hnf4a locus during aging is achieved especially by recruitment of H3K27me3.