DEVELOPMENTAL EXPRESSION OF THE MATERNAL PROTEIN XDCOH, THE DIMERIZATION COFACTOR OF THE HOMEOPROTEIN LFB1 (HNF1)

The tissue-specific transcription factors LFB1 (HNF1) and LFB3 (vHNF1) mainly expressed in liver, kidney and intestine are homeoproteins tha t interact with the regulatory element HP1. The HP1 sequence constitut es one of the most important cis-acting elements in liver-specifically expressed genes, while its function in other cell types containing LF B1 and LFB3 is not fully understood. In mammals, LFB1 activity is modu lated by DCoH, a cofactor that stimulates the LFB1 transactivation sig nificantly. Using the rat cDNA probe, we cloned the corresponding Xeno pus sequence XDCoH, encoding a 104 amino acid protein, that is 85% ide ntical to the rat protein. XDCoH enhances the LFB1-dependent transacti vation potential in transfection experiments and interacts in vitro di rectly with LFB1 and its variant form LFB3. The protein is detectable in liver and kidney extracts of adult frogs and in small amounts also in lung and stomach, organs expressing LFB1 and/or LFB3 protein as wel l. To investigate the possible involvement of XDCoH in Xenopus develop ment, we analyzed its temporal and spatial expression pattern during e arly embryogenesis. XDCoH is a maternal factor, although LFB1 is absen t in the egg. In early cleavage stages, the protein is detectable in t he cytoplasm of each blastomere and enters the nuclei of the cells as early as the zygotic transcription in the Xenopus embryo starts. The a mount of XDCoH increases dramatically following neurulation, when the formation of liver, pronephros and other organs takes place. Whole-mou nt immunostaining demonstrates that, in the developing larvae, XDCoH i s localized in the nuclei of the hepatocytes, the gut cells and the pr onephric cells, tissues of mesodermal and endodermal origin known to c ontain LFB1 and LFB3. Surprisingly it is also present in the pigmented epithelium surrounding the eye of the embryo, which is derived from t he anterior part of the ectodermal neural plates and lacks LFB1. The t issue distribution of XDCoH during embryogenesis suggests that XDCoH i s involved in determination and differentiation of various unrelated c ell types. It seems likely that XDCoH interaction is not only essentia l for the function of LFB1 and LFB3 but also for certain other transcr iption factors.