THE PATERNAL ALLELE OF THE H19 GENE IS PROGRESSIVELY SILENCED DURING EARLY MOUSE DEVELOPMENT - THE ACETYLATION STATUS OF HISTONES MAY BE INVOLVED IN THE GENERATION OF VARIEGATED EXPRESSION PATTERNS

Transcriptional silencing can reflect heritable, epigenetic inactivati on of genes, either singly or in groups, during the life-time of an or ganism. This phenomenon is exemplified by parent-of-origin-specific in activation events (genomic imprinting) for a subset of mammalian autos omal genes, such as H19, Very little is known, however, about the timi ng and mechanism(s) of silencing of the paternal H19 allele during mou se development, Using a novel in situ approach, we present evidence th at the silencing of the paternal H19 allele is progressive in the trop hectodermal lineage during early mouse development and generates varie gated expression patterns, The silencing process apparently involves r ecruitment of histone deacetylases since the mosaic paternal-specific H19 expression reappears in trichostatin A-treated mouse conceptuses, undergoing in vitro organogenesis, Moreover, the paternal H19 alleles of PatDup.d7 placentas, in which a region encompassing the H19 locus o f chromosome 7 is bipaternally derived, partially escape the silencing process and are expressed in a variegated manner, We suggest that all ele-specific silencing of H19 share some common features with chromati n-mediated silencing in position-effect variegation.