Analysis of sequence upstream of the endogenous H19 gene reveals elements both essential and dispensable for imprinting.

Molecular and Cellular Biology
Joanne L ThorvaldsenMarisa Bartolomei

Abstract

Imprinting of the linked and oppositely expressed mouse H19 and Igf2 genes requires a 2-kb differentially methylated domain (DMD) that is located 2 kb upstream of H19. This element is postulated to function as a methylation-sensitive insulator. Here we test whether an additional sequence 5' of H19 is required for H19 and Igf2 imprinting. Because repetitive elements have been suggested to be important for genomic imprinting, the requirement of a G-rich repetitive element that is located immediately 3' to the DMD was first tested in two targeted deletions: a 2.9-kb deletion (Delta D MD Delta G) that removes the DMD and G-rich repeat and a 1.3-kb deletion (Delta G) removing only the latter. There are also four 21-bp GC-rich repetitive elements within the DMD that bind the insulator-associated CTCF (CCCTC-binding factor) protein and are implicated in mediating methylation-sensitive insulator activity. As three of the four repeats of the 2-kb DMD were deleted in the initial 1.6-kb Delta DMD allele, we analyzed a 3.8-kb targeted allele (Delta 3.8kb-5'H19), which deletes the entire DMD, to test the function of the fourth repeat. Comparative analysis of the 5' deletion alleles reveals that (i) the G-rich repeat element is dispensable f...Continue Reading

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Citations

Mar 9, 2005·Biochemical and Biophysical Research Communications·Kohji OkamuraTakashi Ito
Jun 19, 2004·Genomics·Raluca I Verona, Marisa S Bartolomei
Dec 21, 2002·Trends in Genetics : TIG·Katharine L Arney
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Jul 12, 2008·Human Molecular Genetics·Nora EngelS Marisa Bartolomei
Sep 18, 2009·Genes & Development·Marisa S Bartolomei
Dec 30, 2009·Molecular and Cellular Biology·Claudia GebertKarl Pfeifer
Jun 2, 2011·Molecular and Cellular Biology·Shu LinMarisa S Bartolomei
Sep 17, 2008·Molecular and Cellular Biology·Nathalie BerteauxEric Adriaenssens
Mar 7, 2007·Molecular and Cellular Biology·Young Soo YoonKarl Pfeifer
May 15, 2004·Molecular and Cellular Biology·Piroska E SzabóJeffrey R Mann
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Raluca I VeronaMarisa S Bartolomei
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Sep 30, 2019·Science China. Life Sciences·Qing LiJinsong Li
Oct 1, 2016·The Journal of Biological Chemistry·Komal RamaniShelly C Lu
May 20, 2020·Disease Models & Mechanisms·Suhee Chang, Marisa S Bartolomei

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