Fig. 2: AD risk enhancers spatially interact with the promoters of BIN1 and RABEP1 and regulate their expression in myeloid cells. | Nature Communications

Fig. 2: AD risk enhancers spatially interact with the promoters of BIN1 and RABEP1 and regulate their expression in myeloid cells.

From: Integration of Alzheimer’s disease genetics and myeloid genomics identifies disease risk regulatory elements and genes

Fig. 2: AD risk enhancers spatially interact with the promoters of BIN1 and RABEP1 and regulate their expression in myeloid cells.

a. (i) AD GWAS association signal in the BIN1 locus. (ii) eQTL signal for BIN1 in monocytes obtained from the Cardiogenics study. (iii) Genes that reside in the locus are plotted. Likely target genes of the highlighted AD risk enhancers are shown in red. The arrow indicates the direction of transcription, while the bar indicates the gene body. (iv) Active enhancers in monocytes are plotted. The height of the bar is proportional to the strength of the epigenomic signal. AD risk enhancers that are prioritized through both Hi–C and SMR approaches are highlighted in red. (v) Promoter-capture Hi–C interactions between the BIN1 promoter and the highlighted AD risk enhancers in monocytes. The depth of the arc is proportional to the strength of the interaction. (vi) AD risk enhancer-target gene interactions predicted by SMR analysis of causal associations between chromatin activity and BIN1 expression in monocytes. The depth of the arc is proportional to the strength of the association. (vii) eQTL signal for BIN1 in macrophages obtained from the Cardiogenics study. (viii) Genes that reside in the locus are plotted. Likely target genes of the highlighted AD risk enhancers are shown in red. The arrow indicates the direction of transcription, while the bar indicates the gene body. (ix) Active enhancer elements in macrophages are plotted. AD risk enhancers that interact with the gene promoter are highlighted in red. (x) Promoter-capture Hi–C interactions between the BIN1 promoter and the highlighted AD risk enhancers in macrophages. The depth of the arc is proportional to the strength of the interaction. Both Hi–C and SMR-predicted interactions are anchored at the AD risk enhancer highlighted. b. (i) AD GWAS association signal in the RABEP1 locus. (ii) eQTL signal for RABEP1 in monocytes obtained from the Cardiogenics study. (iii) Genes that reside in the locus are plotted. Likely target genes of the highlighted AD risk enhancers are shown in red. The arrow indicates the direction of transcription, while the bar indicates the gene body. (iv) Active enhancers in monocytes are plotted. The height of the bar is proportional to the strength of the epigenomic signal. AD risk enhancers that are prioritized through both Hi–C and SMR approaches are highlighted in red. (v) Promoter-capture Hi–C interactions between the RABEP1 promoter and the highlighted AD risk enhancers in monocytes. The depth of the arc is proportional to the strength of the interaction. (vi) AD risk enhancer-target gene interactions predicted by SMR analysis of causal associations between chromatin activity and RABEP1 expression in monocytes. The depth of the arc is proportional to the strength of the association. vii) eQTL signal for RABEP1 in macrophages obtained from the Cardiogenics study. (viii) Genes that reside in the locus are plotted.Target genes of the highlighted AD risk enhancers are shown in red. The arrow indicates the direction of transcription, while the bar indicates the gene body. (ix) Active enhancer elements in macrophages are plotted. AD risk enhancers that interact with the gene promoter are highlighted in red. (x) Promoter-capture Hi–C interactions between the RABEP1 promoter and the highlighted AD risk enhancers in macrophages. The depth of the arc is proportional to the strength of the interaction. Hi–C and SMR-predicted interactions are anchored at the AD risk enhancers highlighted.

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