Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis

Webster, KE; O&#39;Bryan, MK; Fletcher, S; Crewther, PE; Aapola, U; Craig, J; Harrison, DK; Aung, H; Phutikanit, N; Lyle, R; Meachem, SJ; Antonarakis, SE; de Krester, DM; Hedger, MP; Peterson, P; Carroll, BJ; Scott, HS

Author(s): Webster, KE; O'Bryan, MK; Fletcher, S; Crewther, PE; Aapola, U; Craig, J; Harrison, DK; Aung, H; Phutikanit, N; Lyle, R; Meachem, SJ; Antonarakis, SE; de Krester, DM; Hedger, MP; Peterson, P; Carroll, BJ; Scott, HS;
Details: Publication Year 2005-03-15,Volume 102,Issue #11,Page 4068-4073
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
Abstract: The production of mature germ cells capable of generating totipotent zygotes is a highly specialized and sexually dimorphic process. The transition from diploid primordial germ cell to haploid spermatozoa requires genome-wide reprogramming of DNA methylation, stage- and testis-specific gene expression, mitotic and meiotic division, and the histone-protamine transition, all requiring unique epigenetic control. Dnmt3L, a DNA methyltransferase regulator, is expressed during gametogenesis, and its deletion results in sterility. We found that during spermatogenesis, Dnmt3L contributes to the acquisition of DNA methylation at paternally imprinted regions, unique nonpericentric heterochromatic sequences, and interspersed repeats, including autonomous transposable elements. We observed retrotransposition of an LTR-ERV1 element in the DNA from Dnmt3L(-/-) germ cells, presumably as a result of hypomethylation. Later in development, in Dnmt3L(-/-) meiotic spermatocytes, we detected abnormalities in the status of biochemical markers of heterochromatin, implying aberrant chromatin packaging. Coincidentally, homologous chromosomes fail to align and form synaptonemal complexes, spermatogenesis arrests, and spermatocytes are lost by apoptosis and sloughing. Because Dnmt3L expression is restricted to gonocytes, the presence of defects in later stages reveals a mechanism whereby early genome reprogramming is linked inextricably to changes in chromatin structure required for completion of spermatogenesis.
Publisher: NATL ACAD SCIENCES
Keywords: DNA METHYLATION; MAMMALIAN DEVELOPMENT; GERM-CELLS; DNMT3L; MEIOSIS; METHYLTRANSFERASES; HETEROCHROMATIN; CHROMOSOMES; COMPONENT; IMPRINTS
Publisher's Version: https://doi.org/10.1073/pnas.0500702102
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2005-03-15 12:00:00