Involvement of a nuclear matrix association region in the regulation of the SPRR2A keratinocyte terminal differentiation marker

The small proline-rich protein genes (SPRRs) code for precursors of the cor nified cell envelope, and are specifically expressed during keratinocyte te rminal differentiation. The single intron of SPRR2A enhanced the activity o f the SPRR2A promoter in transient transfection assays. This enhancement wa s position dependent, and did not function in combination with a heterologo us promoter, indicating that the intron does not contain a classical enhanc er, and that the enhancement was not due to the splicing reaction per se. M ild DNAse-1 digestion of nuclei showed the SPRR2 genes to be tightly associ ated with the nuclear matrix, in contrast to the other cornified envelope p recursor genes mapping to the same chromosomal location (epidermal differen tiation complex). In vitro binding studies indicated that both the proximal promoter and the intron of SPRR2A are required for optimal association of this gene with nuclear matrices. Neither nuclear matrix association nor the relative transcriptional enhancement by the intron changed during keratino cyte differentiation. Apparently the association of the SPRR2A gene with th e nuclear matrix results in a general, differentiation-independent enhancem ent of gene expression.