Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2006-10-13
pubmed:abstractText
The mouse Kcnq1 imprinted domain is located on distal chromosome 7 and contains several imprinted genes that are paternally repressed. Repression of these genes is regulated by a non-coding antisense transcript, Kcnq1ot1, which is paternally expressed. Maternal repression of Kcnq1ot1 is controlled by DNA methylation originating in the oocyte. Some genes in the region are imprinted only in the placenta, whereas others are imprinted in both extra-embryonic and embryonic lineages. Here, we show that Kcnq1ot1 is paternally expressed in preimplantation embryos from the two-cell stage, and that ubiquitously imprinted genes proximal to Kcnq1ot1 are already repressed in blastocysts, ES cells and TS cells. Repressive histone marks such as H3K27me3 are present on the paternal allele of these genes in both ES and TS cells. Placentally imprinted genes that are distal to Kcnq1ot1, by contrast, are not imprinted in blastocysts, ES or TS cells. In these genes, paternal silencing and differential histone marks arise during differentiation of the trophoblast lineage between E4.5 and E7.5. Our findings show that the dynamics during preimplantation development of gene inactivation and acquisition of repressive histone marks in ubiquitously imprinted genes of the Kcnq1 domain are very similar to those of imprinted X inactivation. By contrast, genes that are only imprinted in the placenta, while regulated by the same non-coding RNA transcript Kcnq1ot1, undergo epigenetic inactivation during differentiation of the trophoblast lineage. Our findings establish a model for how epigenetic gene silencing by non-coding RNA may depend on distance from the non-coding RNA and on lineage and differentiation specific factors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4203-10
pubmed:meshHeading
pubmed-meshheading:17021040-Alleles, pubmed-meshheading:17021040-Animals, pubmed-meshheading:17021040-Blastocyst, pubmed-meshheading:17021040-Cell Differentiation, pubmed-meshheading:17021040-Cell Lineage, pubmed-meshheading:17021040-DNA Methylation, pubmed-meshheading:17021040-Embryonic Stem Cells, pubmed-meshheading:17021040-Epigenesis, Genetic, pubmed-meshheading:17021040-Gene Expression Regulation, Developmental, pubmed-meshheading:17021040-Gene Silencing, pubmed-meshheading:17021040-Genomic Imprinting, pubmed-meshheading:17021040-Histones, pubmed-meshheading:17021040-KCNQ1 Potassium Channel, pubmed-meshheading:17021040-Mice, pubmed-meshheading:17021040-Mice, Inbred C57BL, pubmed-meshheading:17021040-Oligonucleotides, Antisense, pubmed-meshheading:17021040-Placenta, pubmed-meshheading:17021040-Trophoblasts, pubmed-meshheading:17021040-X Chromosome Inactivation
pubmed:year
2006
pubmed:articleTitle
Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo.
pubmed:affiliation
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't