60 YEARS OF POMC: Transcriptional and epigenetic regulation of POMC gene expression

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   Figure 1

   Regulatory sequences of the POMC gene. In addition to the promoter, three enhancer sequences contribute to either pituitary or hypothalamic expression of POMC. The diagrams depict current knowledge on DNA binding transcription factors acting on these enhancers. (A) The rat –300 bp POMC enhancer has been the most used to dissect these regulatory sequences, whereas most in vivo data (i.e. ChIP-seq, Fig. 2) are for the mouse enhancer. These sequences are well-conserved, except for a 26 bp insertion in the rat compared with mouse sequences; positions shown on the diagram are for the rat sequence. Transcription factors known to bind the enhancer and to regulate POMC transcription are represented by pictograms on the enhancer. Coactivators that are recruited to these TFs are not shown here for clarity, but they are discussed in the text. (B) The mouse –7 kb enhancer is represented with known binding TFs together with predicted transcription factor binding sites (TFBS). (C) The mouse hypothalamic enhancer is constituted of two subenhancers named nPE1 and nPE2. The diagram represents transcription factors shown to bind the enhancer together with predicted transcription factor binding sites.
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   Figure 2

   The mouse POMC locus. In vivo occupancy of the mouse POMC locus by different transcription factors, the coactivator p300 and RNA polymerase II (RNApol II) is revealed by ChIP-seq. ChIP-seq profiles for the indicated factors are shown above diagrams showing mouse chromosomal positions (mm10) on chromosome 12, the POMC locus together with a plot of mammalian conservation for this locus. ChIP-seq data are from the author's laboratory except Ascl1 data recomputed from Zhang et al. (2015).
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   Figure 3

   Pioneer factor action of Pax7 opens new enhancer repertoire for implementation of the melanotroph gene expression program. (A) Schematic representation of chromatin remodeling exerted by Pax7 at melanotroph-specific enhancers. (B) The PC2 gene –146 kb enhancer is remodeled by Pax7 to allow Tpit binding and enhancer activity. ChIP-seq profiles illustrate the changes in transcription factor occupancy and chromatin state at the –146 kb PC2 enhancer before and after Pax7.

• © 2016 Society for Endocrinology