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 inactivation of genes, either singly or in groups, during the life-time of an organism. This phenomenon is exemplified by parent-of-origin-specific inactivation events (genomic imprinting) for a subset of mammalian autosomal genes, such as H19. Very little is known, however, about the timing and mechanism(s) of silencing of the paternal H19 allele during mouse development. Using a novel in situ approach, we present evidence that the silencing of the paternal H19 allele is progressive in the trophectodermal lineage during early mouse development and generates variegated expression patterns. The silencing process apparently involves recruitment 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 of chromosome 7 is bipaternally derived, partially escape the silencing process and are expressed in a variegated manner. We suggest that allele-specific silencing of H19 share some common features with chromatin-mediated silencing in position-effect variegation.
Svensson
K
K
Department of Animal Development and Genetics, Uppsala University, Sweden.
Mattsson
R
R
James
T C
TC
Wentzel
P
P
Pilartz
M
M
MacLaughlin
J
J
Miller
S J
SJ
Olsson
T
T
Eriksson
U J
UJ
Ohlsson
R
R
D000107:Acetylation; D000483:Alleles; D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D005838:Genotype; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D017403:In Situ Hybridization; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics*; D010641:Phenotype; D010920:Placenta / Q000166:cytology; D012313:RNA / Q000032:analysis; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D004791:Enzyme Inhibitors; C094335:H19 long non-coding RNA; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C012589:trichostatin A; D012313:RNA; D006655:Histone Deacetylases