Fig. 1: The downstream cPcdh superTAD boundary comprises clustered enhancers for Pcdhβγ gene regulation. | Nature Communications

Fig. 1: The downstream cPcdh superTAD boundary comprises clustered enhancers for Pcdhβγ gene regulation.

From: Outward-oriented sites within clustered CTCF boundaries are key for intra-TAD chromatin interactions and gene regulation

Fig. 1: The downstream cPcdh superTAD boundary comprises clustered enhancers for Pcdhβγ gene regulation.The alternative text for this image may have been generated using AI.

a Schematics of the mouse cPcdh locus. The mouse Pcdh α, β, and γ gene clusters are closely-linked within the cPcdh superTAD, which is divided into two TADs of Pcdhα and Pcdhβγ. Pcdh α and γ gene clusters contain 14 and 22 variable first exons, respectively, each of which is alternatively spliced to a single set of three downstream constant exons. The Pcdhβ gene cluster contains 22 variable exons but with no constant exon. Two Pcdhα enhancers, HS5-1 and HS7, are indicated by vertical black arrows. b ChIP-seq of CTCF, Rad21, H3K27ac, and H3K4me1 as well as ATAC-seq profiles of the cPcdh locus in the mouse neocortex. Arrowheads indicate CBS elements with orientations. Within the Pcdhα TAD, each Pcdhα alternate promoter is flanked by two forward CBS elements, the downstream enhancer of HS5-1 is flanked by two reverse CBS elements. Within the Pcdhβγ TAD, each Pcdh β or γ promoter is associated with one forward CBS, except for β1, γc4, and γc5 which have no CBS, as well as γc3 which has two forward CBS elements. c Close-up of the cPcdh superTAD downstream boundary marked by a red dotted rectangle in (a, b). This boundary comprises eight CBS elements, of which only CBSf is in the reverse orientation, and six ATAC-seq peaks, of which HS7L, HS5-1bL, HS18, and HS19-20 are knocked out individually or in combinations in mice. HS5-1aL is mutated at the CBSa motif (mCBSa) due to its location in the coding region. d–k Expression levels of members of the Pcdh β and γ gene clusters in the mouse neocortex from ΔHS7L, mCBSa, ΔHS5-1bL-HS20, ΔHS5-1bL-HS18, ΔHS18-20, ΔHS5-1bL, ΔHS18, or ΔHS19-20 homozygous mice compared to their wild-type (WT) littermates. FPKM, fragments per kilobase of exon per million fragments mapped. Data as mean ± SD; two-tailed Student’s t test. *p < 0.05, **p < 0.01, ***p < 0.001. For each mouse line, n = 4 biologically independent samples; for their WT littermate controls, n = 2. Source data are provided as a Source Data file.

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