Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells

Guangjin Pan; Shulan Tian; Jeff Nie; Chuhu Yang; Victor Ruotti; Hairong Wei; Gudrun A. Jonsdottir; Ron Stewart; James A. Thomson

doi:10.1016/j.stem.2007.08.003

Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells

Guangjin Pan, Shulan Tian, Jeff Nie, Chuhu Yang, Victor Ruotti, Hairong Wei, Gudrun A. Jonsdottir, Ron Stewart, James A. Thomson

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

We mapped Polycomb-associated H3K27 trimethylation (H3K27me3) and Trithorax-associated H3K4 trimethylation (H3K4me3) across the whole genome in human embryonic stem (ES) cells. The vast majority of H3K27me3 colocalized on genes modified with H3K4me3. These comodified genes displayed low expression levels and were enriched in developmental function. Another significant set of genes lacked both modifications and was also expressed at low levels in ES cells but was enriched for gene function in physiological responses rather than development. Comodified genes could change expression levels rapidly during differentiation, but so could a substantial number of genes in other modification categories. SOX2, POU5F1, and NANOG, pluripotency-associated genes, shifted from modification by H3K4me3 alone to colocalization of both modifications as they were repressed during differentiation. Our results demonstrate that H3K27me3 modifications change during early differentiation, both relieving existing repressive domains and imparting new ones, and that colocalization with H3K4me3 is not restricted to pluripotent cells.

Original language	English (US)
Pages (from-to)	299-312
Number of pages	14
Journal	Cell Stem Cell
Volume	1
Issue number	3
DOIs	https://doi.org/10.1016/j.stem.2007.08.003
State	Published - Sep 13 2007

Keywords

STEMCELL

ASJC Scopus subject areas

Molecular Medicine
Genetics
Cell Biology

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10.1016/j.stem.2007.08.003

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@article{d96b1b9c64bb494081d0c0e0cfb04e05,

title = "Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells",

abstract = "We mapped Polycomb-associated H3K27 trimethylation (H3K27me3) and Trithorax-associated H3K4 trimethylation (H3K4me3) across the whole genome in human embryonic stem (ES) cells. The vast majority of H3K27me3 colocalized on genes modified with H3K4me3. These comodified genes displayed low expression levels and were enriched in developmental function. Another significant set of genes lacked both modifications and was also expressed at low levels in ES cells but was enriched for gene function in physiological responses rather than development. Comodified genes could change expression levels rapidly during differentiation, but so could a substantial number of genes in other modification categories. SOX2, POU5F1, and NANOG, pluripotency-associated genes, shifted from modification by H3K4me3 alone to colocalization of both modifications as they were repressed during differentiation. Our results demonstrate that H3K27me3 modifications change during early differentiation, both relieving existing repressive domains and imparting new ones, and that colocalization with H3K4me3 is not restricted to pluripotent cells.",

keywords = "STEMCELL",

author = "Guangjin Pan and Shulan Tian and Jeff Nie and Chuhu Yang and Victor Ruotti and Hairong Wei and Jonsdottir, {Gudrun A.} and Ron Stewart and Thomson, {James A.}",

note = "Funding Information: We thank Palmer Yu and Garrett Lee for technical support and Deborah Faupel for critical reading of the manuscript. We thank Karen Jenny Heidarsdottir and Bryndis Krogh Gisladottir for producing the microarray data. We thank Bing Ren for sharing H3K4me3 HeLa validation data prior to publication and for comments on the manuscript. This work was supported by funding from private donations, the W.M. Keck Foundation, and the WiCell Research Institute. Please address G.P. with requests for materials. J.A.T. is a cofounder and shareholder of Cellular Dynamics International and Stem Cell Products, Inc. ",

year = "2007",

month = sep,

day = "13",

doi = "10.1016/j.stem.2007.08.003",

language = "English (US)",

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journal = "Cell Stem Cell",

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T1 - Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells

AU - Pan, Guangjin

AU - Tian, Shulan

AU - Nie, Jeff

AU - Yang, Chuhu

AU - Ruotti, Victor

AU - Wei, Hairong

AU - Jonsdottir, Gudrun A.

AU - Stewart, Ron

AU - Thomson, James A.

N1 - Funding Information: We thank Palmer Yu and Garrett Lee for technical support and Deborah Faupel for critical reading of the manuscript. We thank Karen Jenny Heidarsdottir and Bryndis Krogh Gisladottir for producing the microarray data. We thank Bing Ren for sharing H3K4me3 HeLa validation data prior to publication and for comments on the manuscript. This work was supported by funding from private donations, the W.M. Keck Foundation, and the WiCell Research Institute. Please address G.P. with requests for materials. J.A.T. is a cofounder and shareholder of Cellular Dynamics International and Stem Cell Products, Inc.

PY - 2007/9/13

Y1 - 2007/9/13

N2 - We mapped Polycomb-associated H3K27 trimethylation (H3K27me3) and Trithorax-associated H3K4 trimethylation (H3K4me3) across the whole genome in human embryonic stem (ES) cells. The vast majority of H3K27me3 colocalized on genes modified with H3K4me3. These comodified genes displayed low expression levels and were enriched in developmental function. Another significant set of genes lacked both modifications and was also expressed at low levels in ES cells but was enriched for gene function in physiological responses rather than development. Comodified genes could change expression levels rapidly during differentiation, but so could a substantial number of genes in other modification categories. SOX2, POU5F1, and NANOG, pluripotency-associated genes, shifted from modification by H3K4me3 alone to colocalization of both modifications as they were repressed during differentiation. Our results demonstrate that H3K27me3 modifications change during early differentiation, both relieving existing repressive domains and imparting new ones, and that colocalization with H3K4me3 is not restricted to pluripotent cells.

AB - We mapped Polycomb-associated H3K27 trimethylation (H3K27me3) and Trithorax-associated H3K4 trimethylation (H3K4me3) across the whole genome in human embryonic stem (ES) cells. The vast majority of H3K27me3 colocalized on genes modified with H3K4me3. These comodified genes displayed low expression levels and were enriched in developmental function. Another significant set of genes lacked both modifications and was also expressed at low levels in ES cells but was enriched for gene function in physiological responses rather than development. Comodified genes could change expression levels rapidly during differentiation, but so could a substantial number of genes in other modification categories. SOX2, POU5F1, and NANOG, pluripotency-associated genes, shifted from modification by H3K4me3 alone to colocalization of both modifications as they were repressed during differentiation. Our results demonstrate that H3K27me3 modifications change during early differentiation, both relieving existing repressive domains and imparting new ones, and that colocalization with H3K4me3 is not restricted to pluripotent cells.

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Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells

Abstract

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