Methylation of histone tails has been implicated in long-term epigenetic memory. Methylated H3 Lys 4 (K4) is a generally conserved mark for euchromatic, transcriptionally active regions, although the effect of this modification is likely also to depend on its distribution both within the euchromatic region and more specifically within a given gene. Here we describe a profile of H3K4 di-methylation that is specific for monoallelically expressed genes. Both X-linked genes subject to X-inactivation and autosomal imprinted genes have di-methylated H3K4 restricted to their promoter regions. In contrast, high levels of H3K4 di-methylation are found in both promoters and exonic parts of autosomal genes and of X-linked genes that escape X-inactivation. We suggest that this pattern of promoter restricted H3 Lys 4 di-methylation, already present in totipotent cells, is causally related to the long-term programming of allelic expression and provides an epigenetic mark for monoallelically expressed genes.