Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [ChIP-seq]

Eukaryotic DNA is packaged into chromatin in the nucleus, which restricts the binding of transcription factors (TFs) to the target DNA sites. FOXA1 functions as a pioneer TF to bind condensed chromatin and initiates the opening of local chromatin for gene expression. However, the principles of how FOXA1 recruits to and unpacks the condensed chromatin remain elusive. Here, we revealed that FOXA1 intrinsically undergoes phase separation through its N-PrLD and C-IDR regions, identified as phase separation region (PSR). Notably, the phase separation property confers FOXA1 the ability to dissolve the chromatin condensates. In addition, the DNA-binding capacity of FOXA1 contributes to its phase separation property. Further genome-wide investigation showed that FOXA1 is recruited to and unpacks the condensed chromatin by its PSR to regulate the function of breast cancer cells. This work provides a principal example of how pioneer TFs function to initiate competent chromatin states by phase separation. ChIP-seq,ATAC-seq and RNA-seq for vector,overexpress FH and FOXA1 in MDA-MB-231 cells