The neuronatin gene resides in a "micro-imprinted" domain on human chromosome 20q11.2

A small fraction of the genome contains genes that are imprinted and thus e xpressed exclusively from one parental allele. We report here that the huma n neuronatin gene (NNAT) on chromosome 20q11.2 is imprinted and transcribed specifically from the paternal allele. The region containing NNAT has mult iple CpG islands, and methylation analysis showed that a 1.8-kb CpG island in its promoter region exhibits differential methylation in all tissues exa mined. This finding is consistent with the island acting as a component of the NNAT imprint control domain. NNAT lies within the singular 8.3-kb intro n of the gene encoding bladder cancer-associated protein (BLCAP), which, as we demonstrate, is not imprinted. This study provides the first example, t o our knowledge, in humans of an imprinted gene contained within the genomi c structure of a nonimprinted gene. Thus, NNAT is in an imprinted "microdom ain," making this locus uniquely suited for the investigation of mechanisms of localized imprint regulation.