Repression of the nonclassical MHC class I gene H2-M1 by cis-acting silencer DNA elements

Abstract

H2-M1 is a non-classical major histocompatibility complex (MHC) class I gene that is highly divergent from classical class I genes; M1 was the first gene in the recently classified M region of the mouse MHC to be cloned. Although the M1 DNA sequence contains normal splice sites, open reading frames within its exons, and a recognizable promoter, no M1 transcripts were detected in various healthy mouse tissues. However, M1 transcripts were detected in transfected L cells and in vivo in brains of M1 transgenic mice, albeit at very low levels, and the level of expression is correlated with transgene copy number. Analysis of the M1 promoter region identified a competent promoter capable of directing transcription, but whose expression is repressed by two strong upstream silencer elements, one mapping between -184 base pairs (bp) and -266 bp and the other between -1149 bp and -1702 bp. These studies suggest that M1 expression is highly regulated and restricted either temporally or to a very limited number of cell types.