IRX5 promotes DNA damage repair and activation of hair follicle stem cells [ATAC-Seq]

Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation. Overall design: HFSC (Ly-6A/E- CD34+ CD45f+) were FACS sorted and lysed. Nuclei were incubated in 50uL of Tn5 transposition buffer for 30mins at 37C. DNA isolation was preformed with Qiagen MinElute Cleanup kit. Library preparation with Illumina TrueSeq library preparation kit and paired end Illumina HiSeq 2500 sequencing (80million reads per sample) was performed at the University of California, Irvine High Throughput Genomics Facility.