707 Chromatin remodeler Lymphoid-specific helicase (Lsh) is a critical determinant controlling postnatal epidermal growth, differentiation and response to injury

In the epidermis, progenitor cells residing in the basal layer proliferate and differentiate, forming multi-layered epithelium. Execution of cell type–specific differentiation program in multi-potent progenitor cells requires a high degree of coordination between the distinct levels of chromatin organization including covalent DNA/histone modifications and higher-order chromatin remodeling. Lsh, a member of the SNF2 chromatin-remodelling family is involved in the control of DNA methylation patterns during embryonic development. Here, we show that in the skin, the Lsh protein is expressed in the basal epidermal layer and in the hair matrix keratinocytes. Skin obtained from newborn Lsh-null mice that die shortly after birth was grafted onto nude immunodeficient mice and showed significant hyperplasia of the interfollicular epidermis with major alterations in the epidermal structure occurring 3 weeks after grafting. In contrast to WT grafts, the Lsh-null grafts showed dramatic hyperproliferation and thickening of the basal epidermal layer. Global transcriptome profiling revealed a marked decrease in the expression of the keratinocyte-specific genes, including Keratin 10, Loricrin, Involucrin, Filaggrin in the epidermis of Lsh-null grafts compared to controls. However, upregulation of Keratin 16 and 17 was also seen in the epidermis of Lsh-null skin versus controls. Lsh ChIP-seq data revealed its binding to numerous target genes including those that control epidermal proliferation and differentiation. Furthermore, Lsh-null skin grafts showed accelerated regeneration after wounding compared to WT controls. These data suggest Lsh as an essential chromatin regulator controlling epidermal proliferation, differentiation and response to injury in postnatal skin.