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. Author manuscript; available in PMC: 2015 Oct 19.
Published in final edited form as: Nat Rev Genet. 2014 Mar 11;15(4):234–246. doi: 10.1038/nrg3663

Figure 3. CTCF regulates enhancer-promoter interactions in a multi-gene cluster.

Figure 3

The human Pcdhα gene cluster contains 13 similar, tandemly arranged, variable first exons (1 to 13, shown in blue if they are transcribed or in white if they are not) and two related c-type ubiquitous first exons (c1 and c2, shown in yellow). Each of these 15 variable first exons is adjacent to its own promoter and is spliced to three downstream constant exons (1 to 3, shown in black). Pcdhα alternate isoforms are expressed stochastically, whereas all the c-type isoforms are expressed ubiquitously in all cells. The SK-N-SH cells depicted here express isoforms 4, 8 and 12. Promoter choice and the formation of an active chromatin hub is mediated by CTCF-cohesin DNA looping between the distal HS5-1 enhancer and distinct promoters at the Pcdhα gene cluster. Individual variable exons (blue and white rectangles) or ubiquitous exons (yellow rectangles) may be expressed and joined to the three exons from the constant region (black rectangles) by pre-mRNA splicing. Binding of CTCF to the promoter preceding individual exons is correlated with the level of gene activity. The active promoters are distinguished from the inactive promoters by an enrichment for H3K4me3 and a depletion of DNA methylation, which leads to expression of the downstream genes (blue rectangles).