<p>The role of non-coding variants in polygenic skin disease and their connection to homeostatic transcription factors (TFs) in epidermis was investigated. Homeostatic TFs were identified by perturb-seq in differentiating keratinocytes, using either 10x or split-pool approaches to sequencing, with follow-up validation by siRNA and RNA-seq. TF binding events were profiled by population sampling Cleavage Under Targets &#x26; Release Using Nuclease (CUT&#x26;RUN), in which a random population of neonatal foreskin keratinocytes were assayed by CUT&#x26;RUN for homeostatic TFs under progenitor growth and differentiation conditions. Heterozygous alleles were identified from the TF binding data and examined for allele specific binding events (ASBs). ASBs were then compared with non-coding variants linked to skin disease. Variants with potentially pathogenic effects were identified. Promoters and high TF occupancy genomic regions were found to be "buffered" against variants causing ASBs.</p>

Disease-Linked Regulatory DNA Variants and Homeostatic Transcription    Factors in Epidermis

Keratinocytes study with OTHER, RNA-Seq data on dbGaP (25 participants)