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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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H3K4me3 and H3K27me3 enrichment profiles on genes expressed in the ICM and the TE.(A) µChIP-chip data of H3K4me3 and H3K27me3 enrichment profiles on promoters of indicated genes in the ICM and TE (log2 ChIP/input ratios). (B) Expression scoring and pattern of each gene examined in (A) in the ICM (Var., variable expression level; Const., consistent expression pattern). Data were extracted from published Affymetrix data [27]. (C) µChIP-qPCR analysis of H3K4me3 and H3K27me3 enrichment on the promoter of Oct4, Nanog and Hhex in the ICM and TE. (D) Percentage of expressed genes with promoters enriched in H3K4me3, H3K4/K27me3 or H3K27me3. Data were extracted from the Affymetrix dataset referred to in (B).
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pone-0009150-g003: H3K4me3 and H3K27me3 enrichment profiles on genes expressed in the ICM and the TE.(A) µChIP-chip data of H3K4me3 and H3K27me3 enrichment profiles on promoters of indicated genes in the ICM and TE (log2 ChIP/input ratios). (B) Expression scoring and pattern of each gene examined in (A) in the ICM (Var., variable expression level; Const., consistent expression pattern). Data were extracted from published Affymetrix data [27]. (C) µChIP-qPCR analysis of H3K4me3 and H3K27me3 enrichment on the promoter of Oct4, Nanog and Hhex in the ICM and TE. (D) Percentage of expressed genes with promoters enriched in H3K4me3, H3K4/K27me3 or H3K27me3. Data were extracted from the Affymetrix dataset referred to in (B).

Mentions: We next examined H3K4me3 and H3K27me3 profiles on promoters of genes reported to be expressed in the ICM and/or in the TE (Figure 3A,B) [1], [27]. Among genes expressed in the ICM, Oct4, Sox2, Lifr, Rex1, Klf4 and Stella were either enriched in H3K4me3 relative to genome-average (Oct4, Sox2, Lifr, Klf4) or occupied by H3K4me3 at near genome-average level (Rex1, Stella). These promoters were either strongly hypo-trimethylated on H3K27 (Sox2, Rex1, Klf4, Stella) or harbored low levels of H3K27me3 (Oct4, Lifr). This was consistent with expression of these genes in the ICM, and notably with Oct4 expression in a subpopulation of cells within the ICM [27]. In the TE, some of these genes were also enriched in H3K4me3 (Oct4, Rex1, Klf4, Stella) with enrichment in or low level H3K27me3, while others (Sox2, Lifr) harbored no H3K4me3 but were enriched in H3K27me3. These observations illustrate, therefore, similar H3K4 or H3K27 trimethylation profiles on a subset of genes (e.g., Oct4, Rex1, Klf4 and Stella) in both the ICM and TE despite their distinct expression pattern in these compartments. Others, such as Sox2 and Lifr, harbor H3K4me3 and H4K27me3 profiles that would be anticipated from their expression patterns.


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)

H3K4me3 and H3K27me3 enrichment profiles on genes expressed in the ICM and the TE.(A) µChIP-chip data of H3K4me3 and H3K27me3 enrichment profiles on promoters of indicated genes in the ICM and TE (log2 ChIP/input ratios). (B) Expression scoring and pattern of each gene examined in (A) in the ICM (Var., variable expression level; Const., consistent expression pattern). Data were extracted from published Affymetrix data [27]. (C) µChIP-qPCR analysis of H3K4me3 and H3K27me3 enrichment on the promoter of Oct4, Nanog and Hhex in the ICM and TE. (D) Percentage of expressed genes with promoters enriched in H3K4me3, H3K4/K27me3 or H3K27me3. Data were extracted from the Affymetrix dataset referred to in (B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2818844&req=5

pone-0009150-g003: H3K4me3 and H3K27me3 enrichment profiles on genes expressed in the ICM and the TE.(A) µChIP-chip data of H3K4me3 and H3K27me3 enrichment profiles on promoters of indicated genes in the ICM and TE (log2 ChIP/input ratios). (B) Expression scoring and pattern of each gene examined in (A) in the ICM (Var., variable expression level; Const., consistent expression pattern). Data were extracted from published Affymetrix data [27]. (C) µChIP-qPCR analysis of H3K4me3 and H3K27me3 enrichment on the promoter of Oct4, Nanog and Hhex in the ICM and TE. (D) Percentage of expressed genes with promoters enriched in H3K4me3, H3K4/K27me3 or H3K27me3. Data were extracted from the Affymetrix dataset referred to in (B).
Mentions: We next examined H3K4me3 and H3K27me3 profiles on promoters of genes reported to be expressed in the ICM and/or in the TE (Figure 3A,B) [1], [27]. Among genes expressed in the ICM, Oct4, Sox2, Lifr, Rex1, Klf4 and Stella were either enriched in H3K4me3 relative to genome-average (Oct4, Sox2, Lifr, Klf4) or occupied by H3K4me3 at near genome-average level (Rex1, Stella). These promoters were either strongly hypo-trimethylated on H3K27 (Sox2, Rex1, Klf4, Stella) or harbored low levels of H3K27me3 (Oct4, Lifr). This was consistent with expression of these genes in the ICM, and notably with Oct4 expression in a subpopulation of cells within the ICM [27]. In the TE, some of these genes were also enriched in H3K4me3 (Oct4, Rex1, Klf4, Stella) with enrichment in or low level H3K27me3, while others (Sox2, Lifr) harbored no H3K4me3 but were enriched in H3K27me3. These observations illustrate, therefore, similar H3K4 or H3K27 trimethylation profiles on a subset of genes (e.g., Oct4, Rex1, Klf4 and Stella) in both the ICM and TE despite their distinct expression pattern in these compartments. Others, such as Sox2 and Lifr, harbor H3K4me3 and H4K27me3 profiles that would be anticipated from their expression patterns.

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