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Histone H3 lysine 27 methylation asymmetry on developmentally-regulated promoters distinguish the first two lineages in mouse preimplantation embryos.

Dahl JA, Reiner AH, Klungland A, Wakayama T, Collas P - PLoS ONE (2010)

Bottom Line: The majority of H3K4/K27me3 co-enriched promoters are distinct between the two lineages, primarily due to differences in the distribution of H3K27me3.Derivation of embryonic stem cells leads to significant losses and gains of H3K4/K27me3 co-enriched promoters relative to the ICM, with distinct contributions of (de)methylation events on K4 and K27.Our results show histone trimethylation asymmetry on promoters in the first two developmental lineages, and highlight an epigenetic skewing associated with embryonic stem cell derivation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Basic Medical Sciences, University of Oslo and Norwegian Center for Stem Cell Research, Oslo, Norway.

ABSTRACT
First lineage specification in the mammalian embryo leads to formation of the inner cell mass (ICM) and trophectoderm (TE), which respectively give rise to embryonic and extraembryonic tissues. We show here that this first differentiation event is accompanied by asymmetric distribution of trimethylated histone H3 lysine 27 (H3K27me3) on promoters of signaling and developmentally-regulated genes in the mouse ICM and TE. A genome-wide survey of promoter occupancy by H3K4me3 and H3K27me3 indicates that both compartments harbor promoters enriched in either modification, and promoters co-enriched in trimethylated H3K4 and H3K27 linked to developmental and signaling functions. The majority of H3K4/K27me3 co-enriched promoters are distinct between the two lineages, primarily due to differences in the distribution of H3K27me3. Derivation of embryonic stem cells leads to significant losses and gains of H3K4/K27me3 co-enriched promoters relative to the ICM, with distinct contributions of (de)methylation events on K4 and K27. Our results show histone trimethylation asymmetry on promoters in the first two developmental lineages, and highlight an epigenetic skewing associated with embryonic stem cell derivation.

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H3K27me3 is asymmetrically distributed in the ICM and TE.(A) 2-D scatter plots of averaged MaxTen values for H3K4me3 and H3K27me3 log2 signal intensities in ICM vs. TE. Data points were colored to indicate classification according to the peak calling algorithm to show H3K4me3- or H3K27me3-enriched promoters in all ChIP replicates in the TE (green), the ICM (purple) and common to both lineages (blue). (B) Venn diagram analysis of H3K4me3, H3K27me3 and H3K4/K27me3 promoters in ICM and TE. (C) Percentages of H3K4me3, H3K27me3 and H3K4/K27me3 promoters shared between ICM and TE, or unique to either lineage.
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pone-0009150-g004: H3K27me3 is asymmetrically distributed in the ICM and TE.(A) 2-D scatter plots of averaged MaxTen values for H3K4me3 and H3K27me3 log2 signal intensities in ICM vs. TE. Data points were colored to indicate classification according to the peak calling algorithm to show H3K4me3- or H3K27me3-enriched promoters in all ChIP replicates in the TE (green), the ICM (purple) and common to both lineages (blue). (B) Venn diagram analysis of H3K4me3, H3K27me3 and H3K4/K27me3 promoters in ICM and TE. (C) Percentages of H3K4me3, H3K27me3 and H3K4/K27me3 promoters shared between ICM and TE, or unique to either lineage.

Mentions: We next examined the extent of epigenetic overlap between the ICM and TE. Two-dimensional scatter plots of MaxTen values from H4K3me3 and H3K27me3 signal intensities in the ICM vs. TE (Figure 4A), together with peak identification (Figure 4B) showed greater overlap of H3K4me3 than H3K27me3 between the two lineages. Nearly 80% of H3K4me3 promoters in the ICM or TE were also enriched in H3K4me3 in the other compartment (Figure 4C). However, we found a lower proportion of H3K27me3 promoters (34%) and of H3K4/K27me3 promoters (22%) in the ICM that also contained these marks in the TE (Figure 4C). Therefore, in the blastocyst, H3K4me3 is largely conserved on promoters in both lineages, whereas there is significant asymmetry in the distribution of H3K27me3. This largely contributes to the asymmetry of H3K4/K27me3 promoter distribution between the ICM and TE.


Histone H3 lysine 27 methylation asymmetry on developmentally-regulated promoters distinguish the first two lineages in mouse preimplantation embryos.

Dahl JA, Reiner AH, Klungland A, Wakayama T, Collas P - PLoS ONE (2010)

H3K27me3 is asymmetrically distributed in the ICM and TE.(A) 2-D scatter plots of averaged MaxTen values for H3K4me3 and H3K27me3 log2 signal intensities in ICM vs. TE. Data points were colored to indicate classification according to the peak calling algorithm to show H3K4me3- or H3K27me3-enriched promoters in all ChIP replicates in the TE (green), the ICM (purple) and common to both lineages (blue). (B) Venn diagram analysis of H3K4me3, H3K27me3 and H3K4/K27me3 promoters in ICM and TE. (C) Percentages of H3K4me3, H3K27me3 and H3K4/K27me3 promoters shared between ICM and TE, or unique to either lineage.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2818844&req=5

pone-0009150-g004: H3K27me3 is asymmetrically distributed in the ICM and TE.(A) 2-D scatter plots of averaged MaxTen values for H3K4me3 and H3K27me3 log2 signal intensities in ICM vs. TE. Data points were colored to indicate classification according to the peak calling algorithm to show H3K4me3- or H3K27me3-enriched promoters in all ChIP replicates in the TE (green), the ICM (purple) and common to both lineages (blue). (B) Venn diagram analysis of H3K4me3, H3K27me3 and H3K4/K27me3 promoters in ICM and TE. (C) Percentages of H3K4me3, H3K27me3 and H3K4/K27me3 promoters shared between ICM and TE, or unique to either lineage.
Mentions: We next examined the extent of epigenetic overlap between the ICM and TE. Two-dimensional scatter plots of MaxTen values from H4K3me3 and H3K27me3 signal intensities in the ICM vs. TE (Figure 4A), together with peak identification (Figure 4B) showed greater overlap of H3K4me3 than H3K27me3 between the two lineages. Nearly 80% of H3K4me3 promoters in the ICM or TE were also enriched in H3K4me3 in the other compartment (Figure 4C). However, we found a lower proportion of H3K27me3 promoters (34%) and of H3K4/K27me3 promoters (22%) in the ICM that also contained these marks in the TE (Figure 4C). Therefore, in the blastocyst, H3K4me3 is largely conserved on promoters in both lineages, whereas there is significant asymmetry in the distribution of H3K27me3. This largely contributes to the asymmetry of H3K4/K27me3 promoter distribution between the ICM and TE.

Bottom Line: The majority of H3K4/K27me3 co-enriched promoters are distinct between the two lineages, primarily due to differences in the distribution of H3K27me3.Derivation of embryonic stem cells leads to significant losses and gains of H3K4/K27me3 co-enriched promoters relative to the ICM, with distinct contributions of (de)methylation events on K4 and K27.Our results show histone trimethylation asymmetry on promoters in the first two developmental lineages, and highlight an epigenetic skewing associated with embryonic stem cell derivation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Basic Medical Sciences, University of Oslo and Norwegian Center for Stem Cell Research, Oslo, Norway.

ABSTRACT
First lineage specification in the mammalian embryo leads to formation of the inner cell mass (ICM) and trophectoderm (TE), which respectively give rise to embryonic and extraembryonic tissues. We show here that this first differentiation event is accompanied by asymmetric distribution of trimethylated histone H3 lysine 27 (H3K27me3) on promoters of signaling and developmentally-regulated genes in the mouse ICM and TE. A genome-wide survey of promoter occupancy by H3K4me3 and H3K27me3 indicates that both compartments harbor promoters enriched in either modification, and promoters co-enriched in trimethylated H3K4 and H3K27 linked to developmental and signaling functions. The majority of H3K4/K27me3 co-enriched promoters are distinct between the two lineages, primarily due to differences in the distribution of H3K27me3. Derivation of embryonic stem cells leads to significant losses and gains of H3K4/K27me3 co-enriched promoters relative to the ICM, with distinct contributions of (de)methylation events on K4 and K27. Our results show histone trimethylation asymmetry on promoters in the first two developmental lineages, and highlight an epigenetic skewing associated with embryonic stem cell derivation.

Show MeSH