Extended Data Fig. 2. Detailed analysis of HCFP1 region.

(a) Magnification of the UCSC Genome Browser output from Fig. 1 with multispecies conservation and the three cREs boxed in blue. Green, red, and blue boxes above cREs denote DNAse clusters reported by ENCODE with the number of unique cell lines/tissue in which the cRE has been found open. (b) Chromatin state segmentation of the HCFP1 region in different human tissues and cell lines from CistromeDB^30,31 and ENCODE¹ data. In SK-N-SH neuroblastoma cells (top track), there are uninterrupted stretch enhancer regions 14.8kb in length encompassing cRE3 and 3.4kb in length encompassing cRE1 and cRE2⁸⁷. The active promoter and active transcription chromatin states indicate an overall high regulatory activity of this region in SK-N-SH cells. The largely repressive chromatin state of the corresponding region in a wide range of other tissues and cells (remaining tracks) highlights how cell-type-specific epigenomic states could potentially influence cRE activity and GATA2 expression. DNAJB8, a molecular chaperone not known to be associated with human disease, is not widely transcribed. (c) ChIP-seq results for NR2F1 and GATA3 from published datasets⁵⁸. Blue horizontal bar above the ChIP-seq results indicates the minimal duplication region, and the green, red, and blue squares under the ChIP-seq results indicate the positions of cRE1, cRE2, and cRE3, respectively. NR2F1 shows specific binding to cRE2 in human iPSC-derived neural crest cells. By contrast, GATA2 and its effector transcription factor (TF) GATA3 bind specifically to cRE1 and cRE3, but not to cRE2 in neuroblastoma SK-N-SH and SH-SY5Y cells.