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Epigenetic patterns maintained in early Caenorhabditis elegans embryos can be established by gene activity in the parental germ cells.

Arico JK, Katz DJ, van der Vlag J, Kelly WG - PLoS Genet. (2011)

Bottom Line: Expression in the adult germ cells also correlates with more robust expression in the somatic lineages of the offspring.These results suggest that differential expression in the parental germ lines may provide a potential mechanism for the establishment of parent-of-origin epigenomic content.This content can be maintained and may heritably affect gene expression in the offspring.

View Article: PubMed Central - PubMed

Affiliation: Biology Department, Rollins Research Center, Emory University, Atlanta, Georgia, United States of America.

ABSTRACT
Epigenetic information, such as parental imprints, can be transmitted with genetic information from parent to offspring through the germ line. Recent reports show that histone modifications can be transmitted through sperm as a component of this information transfer. How the information that is transferred is established in the parent and maintained in the offspring is poorly understood. We previously described a form of imprinted X inactivation in Caenorhabditis elegans where dimethylation on histone 3 at lysine 4 (H3K4me2), a mark of active chromatin, is excluded from the paternal X chromosome (Xp) during spermatogenesis and persists through early cell divisions in the embryo. Based on the observation that the Xp (unlike the maternal X or any autosome) is largely transcriptionally inactive in the paternal germ line, we hypothesized that transcriptional activity in the parent germ line may influence epigenetic information inherited by and maintained in the embryo. We report that chromatin modifications and histone variant patterns assembled in the germ line can be retained in mature gametes. Furthermore, despite extensive chromatin remodeling events at fertilization, the modification patterns arriving with the gametes are largely retained in the early embryo. Using transgenes, we observe that expression in the parental germline correlates with differential chromatin assembly that is replicated and maintained in the early embryo. Expression in the adult germ cells also correlates with more robust expression in the somatic lineages of the offspring. These results suggest that differential expression in the parental germ lines may provide a potential mechanism for the establishment of parent-of-origin epigenomic content. This content can be maintained and may heritably affect gene expression in the offspring.

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Transcriptional activity in parental germ cells influences chromatin assembly in the zygote.(A–E) Chromosomes and transgenic arrays in 1–2 cell embryos with DAPI (red), antibody against H3K4me2 (green), and DNA FISH marking the transgene (blue). Arrowheads in all panels mark the Xp; arrows mark the transgenes. (A) X-linked, germline silent pes-10::GFP transgene lacks H3K4me2 on Xm (arrow) in addition to Xp (arrowhead) in embryos. (B) LG V-linked, germline silent mIs10 transgene (arrow) lacks H3K4me2 in embryos. (C) Germline expressing Ex1336 extra-chromosomal transgene (arrows) accumulates H3K4me2 in embryos. (D) Same transgene as in (C), but lacking adult germline expression and lacks H3K4me2 in embryo (arrow). (E) X-linked, germline expressing his-24::GFP transgene accumulates H3K4me2 on Xp in embryo (arrow). Scale bars, 5 um.
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pgen-1001391-g005: Transcriptional activity in parental germ cells influences chromatin assembly in the zygote.(A–E) Chromosomes and transgenic arrays in 1–2 cell embryos with DAPI (red), antibody against H3K4me2 (green), and DNA FISH marking the transgene (blue). Arrowheads in all panels mark the Xp; arrows mark the transgenes. (A) X-linked, germline silent pes-10::GFP transgene lacks H3K4me2 on Xm (arrow) in addition to Xp (arrowhead) in embryos. (B) LG V-linked, germline silent mIs10 transgene (arrow) lacks H3K4me2 in embryos. (C) Germline expressing Ex1336 extra-chromosomal transgene (arrows) accumulates H3K4me2 in embryos. (D) Same transgene as in (C), but lacking adult germline expression and lacks H3K4me2 in embryo (arrow). (E) X-linked, germline expressing his-24::GFP transgene accumulates H3K4me2 on Xp in embryo (arrow). Scale bars, 5 um.

Mentions: Transcriptional regulation in the germ line is poorly understood in most organisms including C. elegans, presenting a major challenge to experimentally modulating the transcriptional activity of endogenous loci. We therefore tested transgenes that exhibit differential germ line transcription properties and chromosome linkage to correlate epigenetic status in adult germ cells with that in the early embryo. We first examined a strain carrying an X-linked repetitive transgene with a GFP reporter driven by a soma-specific promoter [him-5(e1490);axIs36 (pes-10::GFP, dpy-20(e1282)] [41]. This reporter is not normally active in the germ line of either sex, and as reporter transgenes are typically silent in the germ line of C. elegans, no aberrant or ectopic GFP expression was detected in germ cells of this strain (not shown). This transgene is devoid of H3K4me2 during meiosis in the parental germ cells (Figure S2). Combined H3K4me2 antibody/DNA fluorescence in situ hybridization (FISH) analyses showed that H3K4me2 remained strikingly depleted from the transgene region on the Xm in embryos (Figure 5A). Importantly, the absence of H3K4me2 on the Xm transgene was observed through multiple rounds of cell division in the embryo until GFP became detectable in lineages where the pes-10 promoter is active (8–24 cells; not shown). H3K4me2 remained depleted from the transgene in lineages where the promoter is not active until at least the 50 cell stage (not shown). The establishment of a heritable chromatin state in the embryo that correlates with transgene expression in the parental germ line is thus not specific to the sex of the germ line.


Epigenetic patterns maintained in early Caenorhabditis elegans embryos can be established by gene activity in the parental germ cells.

Arico JK, Katz DJ, van der Vlag J, Kelly WG - PLoS Genet. (2011)

Transcriptional activity in parental germ cells influences chromatin assembly in the zygote.(A–E) Chromosomes and transgenic arrays in 1–2 cell embryos with DAPI (red), antibody against H3K4me2 (green), and DNA FISH marking the transgene (blue). Arrowheads in all panels mark the Xp; arrows mark the transgenes. (A) X-linked, germline silent pes-10::GFP transgene lacks H3K4me2 on Xm (arrow) in addition to Xp (arrowhead) in embryos. (B) LG V-linked, germline silent mIs10 transgene (arrow) lacks H3K4me2 in embryos. (C) Germline expressing Ex1336 extra-chromosomal transgene (arrows) accumulates H3K4me2 in embryos. (D) Same transgene as in (C), but lacking adult germline expression and lacks H3K4me2 in embryo (arrow). (E) X-linked, germline expressing his-24::GFP transgene accumulates H3K4me2 on Xp in embryo (arrow). Scale bars, 5 um.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3111476&req=5

pgen-1001391-g005: Transcriptional activity in parental germ cells influences chromatin assembly in the zygote.(A–E) Chromosomes and transgenic arrays in 1–2 cell embryos with DAPI (red), antibody against H3K4me2 (green), and DNA FISH marking the transgene (blue). Arrowheads in all panels mark the Xp; arrows mark the transgenes. (A) X-linked, germline silent pes-10::GFP transgene lacks H3K4me2 on Xm (arrow) in addition to Xp (arrowhead) in embryos. (B) LG V-linked, germline silent mIs10 transgene (arrow) lacks H3K4me2 in embryos. (C) Germline expressing Ex1336 extra-chromosomal transgene (arrows) accumulates H3K4me2 in embryos. (D) Same transgene as in (C), but lacking adult germline expression and lacks H3K4me2 in embryo (arrow). (E) X-linked, germline expressing his-24::GFP transgene accumulates H3K4me2 on Xp in embryo (arrow). Scale bars, 5 um.
Mentions: Transcriptional regulation in the germ line is poorly understood in most organisms including C. elegans, presenting a major challenge to experimentally modulating the transcriptional activity of endogenous loci. We therefore tested transgenes that exhibit differential germ line transcription properties and chromosome linkage to correlate epigenetic status in adult germ cells with that in the early embryo. We first examined a strain carrying an X-linked repetitive transgene with a GFP reporter driven by a soma-specific promoter [him-5(e1490);axIs36 (pes-10::GFP, dpy-20(e1282)] [41]. This reporter is not normally active in the germ line of either sex, and as reporter transgenes are typically silent in the germ line of C. elegans, no aberrant or ectopic GFP expression was detected in germ cells of this strain (not shown). This transgene is devoid of H3K4me2 during meiosis in the parental germ cells (Figure S2). Combined H3K4me2 antibody/DNA fluorescence in situ hybridization (FISH) analyses showed that H3K4me2 remained strikingly depleted from the transgene region on the Xm in embryos (Figure 5A). Importantly, the absence of H3K4me2 on the Xm transgene was observed through multiple rounds of cell division in the embryo until GFP became detectable in lineages where the pes-10 promoter is active (8–24 cells; not shown). H3K4me2 remained depleted from the transgene in lineages where the promoter is not active until at least the 50 cell stage (not shown). The establishment of a heritable chromatin state in the embryo that correlates with transgene expression in the parental germ line is thus not specific to the sex of the germ line.

Bottom Line: Expression in the adult germ cells also correlates with more robust expression in the somatic lineages of the offspring.These results suggest that differential expression in the parental germ lines may provide a potential mechanism for the establishment of parent-of-origin epigenomic content.This content can be maintained and may heritably affect gene expression in the offspring.

View Article: PubMed Central - PubMed

Affiliation: Biology Department, Rollins Research Center, Emory University, Atlanta, Georgia, United States of America.

ABSTRACT
Epigenetic information, such as parental imprints, can be transmitted with genetic information from parent to offspring through the germ line. Recent reports show that histone modifications can be transmitted through sperm as a component of this information transfer. How the information that is transferred is established in the parent and maintained in the offspring is poorly understood. We previously described a form of imprinted X inactivation in Caenorhabditis elegans where dimethylation on histone 3 at lysine 4 (H3K4me2), a mark of active chromatin, is excluded from the paternal X chromosome (Xp) during spermatogenesis and persists through early cell divisions in the embryo. Based on the observation that the Xp (unlike the maternal X or any autosome) is largely transcriptionally inactive in the paternal germ line, we hypothesized that transcriptional activity in the parent germ line may influence epigenetic information inherited by and maintained in the embryo. We report that chromatin modifications and histone variant patterns assembled in the germ line can be retained in mature gametes. Furthermore, despite extensive chromatin remodeling events at fertilization, the modification patterns arriving with the gametes are largely retained in the early embryo. Using transgenes, we observe that expression in the parental germline correlates with differential chromatin assembly that is replicated and maintained in the early embryo. Expression in the adult germ cells also correlates with more robust expression in the somatic lineages of the offspring. These results suggest that differential expression in the parental germ lines may provide a potential mechanism for the establishment of parent-of-origin epigenomic content. This content can be maintained and may heritably affect gene expression in the offspring.

Show MeSH
Related in: MedlinePlus