A mono-allelic bivalent chromatin domain controls tissue-specific imprinting at Grb10.
Genomic imprinting is a developmental mechanism that mediates parent-of-origin-specific expression in a subset of genes. How the tissue specificity of imprinted gene expression is controlled remains poorly understood. As a model to address this question, we studied Grb10, a gene that displays brain-specific expression from the paternal chromosome. Here, we show in the mouse that the paternal promoter region is marked by allelic bivalent chromatin enriched in both H3K4me2 and H3K27me3, from early embryonic stages onwards. This is maintained in all somatic tissues, but brain. The bivalent domain is resolved upon neural commitment, during the developmental window in which paternal expression is activated. Our data indicate that bivalent chromatin, in combination with neuronal factors, controls the paternal expression of Grb10 in brain. This finding highlights a novel mechanism to control tissue-specific imprinting.
Sanz
Lionel A
LA
Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier II, Montpellier, France.
Chamberlain
Stormy
S
Sabourin
Jean-Charles
JC
Henckel
Amandine
A
Magnuson
Terry
T
Hugnot
Jean-Philippe
JP
Feil
Robert
R
Arnaud
Philippe
P
D000483:Alleles; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D051383:GRB10 Adaptor Protein / Q000235:genetics / Q000378:metabolism; D018392:Genomic Imprinting; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology; D063151:Polycomb Repressive Complex 2; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology
D002843:Chromatin; C107275:Eed protein, mouse; D006657:Histones; D012097:Repressor Proteins; D051383:GRB10 Adaptor Protein; D063151:Polycomb Repressive Complex 2