2014
DOI: 10.1101/gad.244848.114
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Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells

Abstract: Transcription of endogenous retroviruses (ERVs) is inhibited by de novo DNA methylation during gametogenesis, a process initiated after birth in oocytes and at approximately embryonic day 15.5 (E15.5) in prospermatogonia. Earlier in germline development, the genome, including most retrotransposons, is progressively demethylated. Young ERVK and ERV1 elements, however, retain intermediate methylation levels. As DNA methylation reaches a low point in E13.5 primordial germ cells (PGCs) of both sexes, we determined… Show more

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Cited by 234 publications
(263 citation statements)
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References 67 publications
(99 reference statements)
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“…As low-input methods are particularly useful for the study of cell types present in limited numbers in vivo, we validated our method on PGCs, the precursors to mature gametes. To determine sexspecific H3K27me3 profiles correlation to sex-specific gene expression, we used ULI-NChIP-seq data sets prepared from 10 3 PGCs purified from the gonads of single male and female E13.5 embryos 19 . Comparison with previously published low-input H3K27me3 data sets generated from 5.2 Â 10 4 to 1.8 Â 10 5 PGCs in two independent studies 12,13 reveals that our method yielded similar or greater sequencing depth while minimizing total duplicate generation (o15%) (Fig.…”
Section: Resultsmentioning
confidence: 99%
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“…As low-input methods are particularly useful for the study of cell types present in limited numbers in vivo, we validated our method on PGCs, the precursors to mature gametes. To determine sexspecific H3K27me3 profiles correlation to sex-specific gene expression, we used ULI-NChIP-seq data sets prepared from 10 3 PGCs purified from the gonads of single male and female E13.5 embryos 19 . Comparison with previously published low-input H3K27me3 data sets generated from 5.2 Â 10 4 to 1.8 Â 10 5 PGCs in two independent studies 12,13 reveals that our method yielded similar or greater sequencing depth while minimizing total duplicate generation (o15%) (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…For example, in our recently published study 19 , only B3 Â 10 3 and B6 Â 10 3 SSEA1 þ PGCs could be purified by fluorescenceactivated cell sorting (FACS) from single male and female wildtype embryos, respectively. In genetically manipulated animals, cell viability can be impacted, decreasing sample yield yet further.…”
Section: Discussionmentioning
confidence: 99%
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“…Indeed, global analysis of RNA-seq data from pro-B cells, ESCs, and primordial germ cells (PGCs) revealed de-repression of different ERV families on Setdb1 deletion (Fig. 3A) (4,15). Loss of SETDB1 induces a robust expression of MLV, MMTV, and VL30 families in pro-B cells.…”
Section: Setdb1 Regulates Ervs In Committed B-lineage Cellsmentioning
confidence: 99%