The role of the SWI/SNF ATP dependent chromatin remodelling complex in the regulation of the human hair follicle cell proliferation and control of the human cutaneous wound healing

Abstract

Epigenetic regulation of gene expression occurs at a number of levels including covalent DNA and histone modifications, nucleosome positioning and ATP-dependent chromatin remodelling as well as higher order chromatin folding and 3D genome organisation. ATP-dependent chromatin remodelling complexes modulate nucleosome structure, positioning and chromatin de-compaction and are involved in gene activation and repression. SWI/SNF ATP-dependent chromatin remodelling complexes contain either BRG1 or BRM as the core ATPase together with other common and variable subunits. BRG1 is required for terminal epidermal differentiation in mice and humans and for hair follicle stem cell activation during mouse hair follicle regeneration and cutaneous wound healing. However, the role of SWI/SNF complexes in human hair growth and wound healing remain unknown. Here it is demonstrated that genes encoding SWI/SNF complex subunits are expressed in human hair follicles. It also highlights that siRNA mediated suppression of SWI/SNF complexes in hair follicle culture has no effect on hair growth, or anagen-catagen transition in the short term, but a significant increase in proliferation of the outer root sheath keratinocytes was seen. The data also documents the expression of several SWI/SNF subunits in human epidermis and that siRNA mediated SMARCA4 gene suppression in primary human keratinocyte monolayers defined the requirements of BRG1 for wound closure through control of cell migration, but not proliferation. In summary, this data revealed a diverse SWI/SNF complex subunit composition in human epidermis and hair follicle, and an essential role of the core complex ATPase BRG1 in keratinocyte migration during wound closure and re-epithelisation.