Fig. 1
bioChIP-seq of major cardiac transcription factors in fetal and adult heart. a Strategy for bioChIP-seq. Murine knock-in alleles fuse a biotin acceptor peptide (BIO) to the C-terminus of target transcription factors (TFs). BirA expressed from the Rosa26 locus modifies BIO with biotin, permitting high affinity pull-down under consistent conditions. b Correlation between aligned bioChIP-seq data obtained from heart ventricles. Fetal (F_; purple) and adult (A_; green) data were acquired in biological duplicates (_1 and _2). Heatmap shows Spearman correlation coefficients for signal within the union of peak regions across all replicates. G, GATA4; A, MEF2A; C, MEF2C; N, NKX2-5; S, SRF; T, TBX5; E, TEAD1. c Dynamic changes in TF binding between fetal and adult stages. Heatmaps of TF-bound regions, arranged into fetal-specific (purple), adult-specific (green), and shared groups (cyan). d Number and location of TF regions with respect to gene annotations. Middle row, regions proximal (within 2 kb) or distal (>2 kb) to the TSS. Bottom row, more detailed genome annotations, using definitions from Homer. “TSS” is defined as 1 kb upstream to 0.1 kb downstream of the TSS. ncRNA, non-coding RNA. See also Supplementary Data 1. e Enriched biological process gene ontology (GO) terms for genes neighboring distal TF-occupied regions, as defined by the default settings of GREAT62. The union of the five most significant terms for the top 1000 distal regions (ranked by BioChIP-seq signal) bound by each TF in fetal or adult stages. Color code indicates manual annotation of sets containing similar GO terms. Gray, non-significant P-value. See Supplementary Data 2 for the full table. f Motifs enriched among the top 1000 distal TF regions (summit ±100 bp). Regions were scanned for TF-binding motifs of the bioChIP’d TFs using Homer. Enrichment P-values (left) and percent positive regions (right) are shown. g Central enrichment plots for the top 1000 distal fetal MEF2A and MEF2C bioChIP-seq regions. MEF2A showed central enrichment for the MEF2 motif and weaker central enrichment for SRF. MEF2C showed central enrichment of TEAD, TBX5, and NKX2-5 that was greater than the MEF2 motif itself. Displayed motifs have E-value < 10-5. Source data for panels d–g are provided as a Source Data file
