Abstract
The promyelocytic leukemia (PML) protein is an essential component of nuclear compartments called PML bodies. This protein participates in several cellular processes, including growth control, senescence, apoptosis, and differentiation. Previous studies have suggested that PML regulates gene expression at a subset of loci through a function in chromatin remodeling. Here we have studied global gene expression patterns in mouse embryonic skin derived from Pml depleted and wild type mouse embryos. Differential gene expression analysis at different developmental stages revealed a key role of PML in regulating genes involved in epidermal stratification. In particular, we observed dysregulation of the late cornified envelope gene cluster, which is a sub-region of the epidermal differentiation complex. In agreement with these data, PML body numbers are elevated in basal keratinocytes during embryogenesis, and we observed reduced epidermal thickness and defective hair follicle development in PML depleted mouse embryos.
Highlights
The promyelocytic leukemia (PML) protein has been implicated in various cellular functions including apoptosis [1], genome maintenance [2,3,4], innate immunity [5,6], and differentiation [7,8,9].A unique feature of PML is its ability to form nuclear compartments called PML bodies [10]
In agreement with a role of PML in epidermal stratification and morphogenesis we show that PML knockout mice exhibit a delayed epidermal stratification and impaired hair follicle development during embryogenesis
Several of the most differentially expressed genes detected by comparing data from wild type and PML depleted mice at different stages of embryogenesis were found to be present within the epidermal differentiation complex (EDC), a gene-rich locus which is known to encode multiple proteins with key functions in epidermal growth and differentiation
Summary
The promyelocytic leukemia (PML) protein has been implicated in various cellular functions including apoptosis [1], genome maintenance [2,3,4], innate immunity [5,6], and differentiation [7,8,9]. By employing RNA-seq analysis of wild type and PML depleted mice at different stages of embryonic development, we identified the epidermal differentiation complex (EDC), a gene cluster with striking structural similarities to the MHC, as one of the most deregulated loci. It comprises 62 coding genes within four gene families: filaggrin and FLG-like, late cornified envelope genes (LCEs), small proline-rich region (SPRRs, including loricrin (LOR) and involucrin (IVL)), and S100 genes [27,28]. The study demonstrates a role of PML in epidermis development during embryogenesis and points to an important role of PML in gene cluster regulation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
