GSE122327
Regulation of human epidermal progenitor cell function by HNRNPK through transcriptional and post-transcriptional mechanisms
Maintenance of high-turnover tissues such as the epidermis requires a tight balance between stem and progenitor cell proliferation and differentiation. The molecular mechanisms governing this process are an area of active investigation. Here we show that HNRNPK, a multifunctional protein, is necessary to prevent premature differentiation and sustains the proliferative capacity of epidermal stem and progenitor cells. To prevent premature differentiation of progenitor cells, HNRNPK recruits DDX6 to a subset of mRNAs that code for transcription factors that induce differentiation. Upon binding, these mRNAs such as GRHL3, KLF4, and ZNF750 are degraded which prevents premature differentiation. To sustain the proliferative capacity of the epidermis, HNRNPK recruits RNA polymerase II to genomic sites of proliferation genes such as MYC, FGFBP1, PTHLH, ITGB4 to promote their expressions. Our study establishes a prominent role for HNRNPK in maintaining adult tissue homeostasis through both transcriptional and post-transcriptional mechanisms. Overall design: HNRNPK RNA-seq in primary keratinocytes. HNRNPK RNA IP-seq in primary keratinocytes. ChIP-seq with HNRNPK and RNA POL II antibodies in primary keratinocytes.