Fig. 2: Parathyroid-specific regulatory elements and chromatin interactions.

a Distinctive open chromatin profiles in parathyroids at the CASR locus. Orange: GCM2 ChIP-seq and DNase-seq for parathyroids. DNase-seq profiles from the ENCODE in two tissues where CASR is also expressed: pancreas (green) and kidney (purple). Two strong DNase-seq peaks bound by GCM2 in the intronic region of CASR (highlighted in gray box) are present only in parathyroids. Y-axis: normalized read densities for GCM2 ChIP-seq and DNA-seq profiles. The scale of the value is indicated in parentheses. b Chromatin interactions between the promoter of CASR and regulatory elements in several tissue types. Purple box, the promoter region of CASR; gray, cis-regulatory regions interacting with the CASR promoter in parathyroid gland tissues (PTG) determined by Hi-C data from PTG (this study). Below are interactions between CASR promoters and distal regions in other tissue types by promoter capture Hi-C. Y-axis for genomic profiles: normalized read densities for GCM2 ChIP-seq, DNase-seq, and CTCF ChIP-seq. The scale of the value is indicated in parentheses. E enhancer element. c Parathyroid enhancer activity validations by luciferase assays in HEK293 and DF-1 cell lines. The enhancer elements were determined by H3K27ac, H3K4me1 and GCM2 signals in parathyroids. n = 4 biologically independent samples; 3 repeated measurements for each biological sample. Rep biological replicate. Distinct dot shapes correspond to distinct samples. P-values were obtained through one-sided Student’s t-tests on 4 biological replicates. The mean of 3 repeated measurements was used for each biological replicate. The bar graph displays the mean values of biological replicates with error bars of ±SEM (standard error of the mean).