International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 177 - COORDINATE REGULATION OF THE MULTI-GENE FAMILY OF SMALL PROLINE RICH PROTEINS

N Martin
NHGRI

Patel S, Segre J
NHGRI

The epidermis is a self-renewing tissue, which provides a natural barrier between the organism and the environment. The cornified cell envelope (CE), proteins assembled and cross-linked beneath the plasma membrane of terminally differentiated cells, is a major element responsible for the protective function of the skin. Our laboratory is interested in the molecular factors and signal transduction pathways governing the establishment of the epidermal barrier.   Mice with a targeted ablation of the transcription factor Klf4 have a specific defect in barrier function.  Transcriptional profiling of the Klf4-/- mice revealed that 11 members of the Small PRoline-Rich protein (SPRR) family are upregulated. The SPRR proteins constitute a specific class of CE precursors encoded by a conserved multigene family clustered within the epidermal differentiation complex at human chromosome 1q21, mouse chromosome 3. The fact that this cluster of genes is so conserved in evolution and that they are all upregulated in the Klf4 -/- mice led us to postulate that the genes may all be held together to enable coordinate gene regulation. We used long-range comparative sequence analysis (PipMaker, rVISTA and TraFaC) to identify conserved noncoding sequences representing candidate transcriptional regulatory element for the Sprr locus. We identified: i) conserved sequences in the promoters, introns and intergenic regions between orthologs, ii) additional conserved DNA sequences between paralogs that could represent species-specific cis-regulatory elements, iii) new Sprr genes in the locus. We are currently generating experimental evidence to assign a function to these putative regulatory regions.


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