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Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally.

Wasson JA, Simon AK, Myrick DA, Wolf G, Driscoll S, Pfaff SL, Macfarlan TS, Katz DJ - Elife (2016)

Bottom Line: Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults.These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes.These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, United States.

ABSTRACT
Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet the identity and function of these maternal factors during the gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this transition by removing H3K4me2 and preventing the transgenerational inheritance of transcription patterns. Here we show that loss of maternal LSD1/KDM1A in mice results in embryonic arrest at the 1-2 cell stage, with arrested embryos failing to undergo the maternal-to-zygotic transition. This suggests that LSD1/KDM1A maternal reprogramming is conserved. Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults. These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes. These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.

No MeSH data available.


Related in: MedlinePlus

The MZT is impaired in Kdm1aZp3 mutants.(A–H) Differential expression of mRNAs in Kdm1afl/fl versus Kdm1aZp3 oocytes (A,E), Kdm1afl/fl M+Z+ versus Kdm1aZp3 M-Z+ 2C embryos (B,F), Kdm1afl/fl M+Z+ 2C embryos versus Kdm1afl/fl oocytes (C,G), and Kdm1aZp3 M-Z+ 2C embryos versus Kdm1afl/fl oocytes (D,H) as determined by RNA-seq. Differential expression represented in mean difference plots (A–D) and normalized FPKM values on XY scatter plots (E–H). Genes/repeats highlighted in red are significant.DOI:http://dx.doi.org/10.7554/eLife.08848.013
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fig3s1: The MZT is impaired in Kdm1aZp3 mutants.(A–H) Differential expression of mRNAs in Kdm1afl/fl versus Kdm1aZp3 oocytes (A,E), Kdm1afl/fl M+Z+ versus Kdm1aZp3 M-Z+ 2C embryos (B,F), Kdm1afl/fl M+Z+ 2C embryos versus Kdm1afl/fl oocytes (C,G), and Kdm1aZp3 M-Z+ 2C embryos versus Kdm1afl/fl oocytes (D,H) as determined by RNA-seq. Differential expression represented in mean difference plots (A–D) and normalized FPKM values on XY scatter plots (E–H). Genes/repeats highlighted in red are significant.DOI:http://dx.doi.org/10.7554/eLife.08848.013


Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally.

Wasson JA, Simon AK, Myrick DA, Wolf G, Driscoll S, Pfaff SL, Macfarlan TS, Katz DJ - Elife (2016)

The MZT is impaired in Kdm1aZp3 mutants.(A–H) Differential expression of mRNAs in Kdm1afl/fl versus Kdm1aZp3 oocytes (A,E), Kdm1afl/fl M+Z+ versus Kdm1aZp3 M-Z+ 2C embryos (B,F), Kdm1afl/fl M+Z+ 2C embryos versus Kdm1afl/fl oocytes (C,G), and Kdm1aZp3 M-Z+ 2C embryos versus Kdm1afl/fl oocytes (D,H) as determined by RNA-seq. Differential expression represented in mean difference plots (A–D) and normalized FPKM values on XY scatter plots (E–H). Genes/repeats highlighted in red are significant.DOI:http://dx.doi.org/10.7554/eLife.08848.013
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829428&req=5

fig3s1: The MZT is impaired in Kdm1aZp3 mutants.(A–H) Differential expression of mRNAs in Kdm1afl/fl versus Kdm1aZp3 oocytes (A,E), Kdm1afl/fl M+Z+ versus Kdm1aZp3 M-Z+ 2C embryos (B,F), Kdm1afl/fl M+Z+ 2C embryos versus Kdm1afl/fl oocytes (C,G), and Kdm1aZp3 M-Z+ 2C embryos versus Kdm1afl/fl oocytes (D,H) as determined by RNA-seq. Differential expression represented in mean difference plots (A–D) and normalized FPKM values on XY scatter plots (E–H). Genes/repeats highlighted in red are significant.DOI:http://dx.doi.org/10.7554/eLife.08848.013
Bottom Line: Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults.These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes.These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, United States.

ABSTRACT
Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet the identity and function of these maternal factors during the gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this transition by removing H3K4me2 and preventing the transgenerational inheritance of transcription patterns. Here we show that loss of maternal LSD1/KDM1A in mice results in embryonic arrest at the 1-2 cell stage, with arrested embryos failing to undergo the maternal-to-zygotic transition. This suggests that LSD1/KDM1A maternal reprogramming is conserved. Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults. These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes. These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.

No MeSH data available.


Related in: MedlinePlus