Figure 3. Proposed simplified model for the enhancer-promoter looping at the Hnf4a locus in young and old C and LP islets. In islets from young adult C rats the enhancer is enriched in active histone marks and interacts closely with the Hnf4a P2 promoter, leading to high levels of P2 transcription. The P2 promoter-enhancer interaction is impaired in islets of animals exposed to a LP diet during early development, due to depletion of active histone marks and enrichment in suppressive histone marks at the enhancer region. Aging associates reduced levels of Hnf4a expression due to enrichment in suppressive histone marks across the locus, which is more pronounced in LP islets. The accumulation of suppressive histone marks might further weaken the P2 promoter-enhancer interaction.