Regulatory elements involved in the liver-specific expression of the mouse MHC class I Q10 gene: characterization of...

The murine MHC genes code for the classical H-2K, D, and L transplantation antigens, and for other class I-like proteins called Qa and TIa molecules. Most of the latter have a restricted tissue distribution whereas classical transplantation antigens are virtually expressed by all somatic cells of the adult organism. Q10 is a Qa region gene, which was found to be expressed in liver and yolk sac, a regulatory pattern more evocative of the expression of a large set of serum proteins secreted by the liver than of a classical class I antigen. First, we have characterized several regions in the promoter of Q10 which bind factors present in liver nuclear extracts. Our most striking observation is that one of these factors, which we named TA-f, binds in the TATA box region of Q10 and Kb and displays tissue-specific expression, in that we found the activity only in liver and kidney. Secondly, we have performed a comparative analysis of the 5' upstream sequences of Q10 with those of H-2Kb, Ld, and other Qa genes. We have shown that most of the regulatory elements involved in the ubiquitous expression of H-2Kb are punctually altered and not functional in Q10. Similarly, most of the binding sequences for liver factors in the Q10 promoter, except the TA region, do not exist in the other H-2 class I genes which, however, have conserved most of the functional regions defined in H-2Kb and Ld. These results suggest that the tissue-specific expression of Q10 is associated with both alteration of the sequences conferring ubiquitous expression to other class I genes and/or creation of new sequences able to bind liver-specific regulatory factors. However, our observations also suggest that a unique sequence, the TATA box, may confer differential regulation in different tissues, since it binds a factor whose expression is restricted to the liver and kidney.