tissues. Early in this terminal pathway of differentia-CL-20 is a novel gene encoding a protein that is struc-tion, cells undergo irreversible growth arrest that is turally related to but distinct from the peripheral myelin accompanied by a down-regulation of several cell cycle protein PMP22. Like PMP22, CL-20 is likely to play im-control genes, including RB and cdc2 (Jetten et al., portant roles in the regulation of cell proliferation, dif-1992; Saunders and Jetten, 1994). This is followed by ferentiation, and cell death. In this study, we describe the induction of differentiation-specific genes such as the cloning and sequencing of a cDNA encoding the hu-expression of several keratins and proteins involved man homologue of CL-20 and characterize the genomic in the formation of the cross-linked envelope such as structure of this gene. The hCL-20 gene (HGMW-ap-transglutaminase type I and cornifins (Eckert and proved symbol EMP1) encodes a protein of 157 amino Rorke, 1989;Jetten et al., 1992;Marvin et al., 1992). et al., 1995), which in several human tissues by Northern analysis. Retinoic might be the rat homologue of CL-20. The rabbit CLacid, which inhibits squamous differentiation, represses 20 exhibits moderate (43%) homology to the human CL-20 expression in normal human bronchial epithelial peripheral myelin protein, PMP22 protein (also known cells. The genomic structure of the hCL-20 gene was ana-as gas3) (Manfioletti et al., 1990; Welcher et al., 1991; lyzed using a P1 vector containing this gene. The hCL- Suter et al., 1992). CL-20, EMP-1, 20 gene contains five exons about 0.2, 0.12, 0.1, 0.14, and and PMP22 exhibit a great structural similarity, sug-2.2 kb and four introns about 15, 1.9, 0