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Developmental cell
Oct, 2008;15 (4): 547-57.

A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints.

Xiajun Li, Mitsuteru Ito, Fen Zhou, Neil Youngson, Xiaopan Zuo, Philip Leder, Anne C Ferguson-Smith
Author Information
  1. Xiajun Li: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. xiajun.li@mssm.edu
PMID: 18854139 DOI: 10.1016/j.devcel.2008.08.014

Abstract

The mechanisms responsible for maintaining genomic methylation imprints in mouse embryos are not understood. We generated a knockout mouse in the Zfp57 locus encoding a KRAB zinc finger protein. Loss of just the zygotic function of Zfp57 causes partial neonatal lethality, whereas eliminating both the maternal and zygotic functions of Zfp57 results in a highly penetrant embryonic lethality. In oocytes, absence of Zfp57 results in failure to establish maternal methylation imprints at the Snrpn imprinted region. Intriguingly, methylation imprints are reacquired specifically at the maternally derived Snrpn imprinted region when the zygotic Zfp57 is present in embryos. This suggests that there may be DNA methylation-independent memory for genomic imprints. Zfp57 is also required for the postfertilization maintenance of maternal and paternal methylation imprints at multiple imprinted domains. The effects on genomic imprinting are consistent with the maternal-zygotic lethality of Zfp57 mutants.

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Grants

  1. G0701196/Medical Research Council
  2. P01 HD047675-01A17046/NICHD NIH HHS
  3. /Biotechnology and Biological Sciences Research Council

MeSH Term

Amino Acid Sequence
Animals
Blastocyst
DNA Methylation
Embryo, Mammalian
Female
Genomic Imprinting
Heterozygote
Homozygote
Immunohistochemistry
Male
Mice
Mice, Knockout
Molecular Sequence Data
Mutation
Nuclear Proteins
Oocytes
Pregnancy
Repressor Proteins
Sequence Homology, Amino Acid
Zinc Fingers
Zygote

Chemicals

Nuclear Proteins
Repressor Proteins
Zfp-57 protein, mouse
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 11

Word Cloud

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