Mass spectrometry identifies and quantifies 74 unique histone H4 isoforms in differentiating human embryonic stem cells

被引：133

作者：

Phanstiel, Doug ^{[1
]}

Brumbaugh, Justin ^{[4
]}

Berggren, W. Travis ^{[7
]}

Conard, Kevin ^{[7
]}

Feng, Xuezhu ^{[3
]}

Levenstein, Mark E. ^{[7
]}

McAlister, Graeme C. ^{[1
]}

Thomson, James A. ^{[3
,5
,6
,7
]}

Coon, Joshua J. ^{[1
,2
]}

机构：

[1] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

[2] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA

[3] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA

[4] Univ Wisconsin, Integrated Program Biochem, Madison, WI 53706 USA

[5] Univ Wisconsin, Genome Ctr Wisconsin, Madison, WI 53706 USA

[6] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA

[7] WiCell Res Inst, Madison, WI 53706 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 11期

关键词：

electron transfer dissociation; epigenetics; posttranslational modification; histone code; pluripotency;

D O I：

10.1073/pnas.0710515105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Epigenetic regulation through chromatin is thought to play a critical role in the establishment and maintenance of pluripotency. Traditionally, antibody-based technologies were used to probe for specific posttranslational modifications (PTMs) present on histone tails, but these methods do not generally reveal the presence of multiple modifications on a single-histone tail (combinatorial codes). Here, we describe technology for the discovery and quantification of histone combinatorial codes that is based on chromatography and mass spectrometry. We applied this methodology to decipher 74 discrete combinatorial codes on the tail of histone H4 from human embryonic stem (ES) cells. Finally, we quantified the abundances of these codes as human ES cells undergo differentiation to reveal striking changes in methylation and acetylation patterns. For example, H4R3 methylation was observed only in the presence of H4K20 dimethylation; such context-specific patterning exemplifies the power of this technique.

引用

页码：4093 / 4098

页数：6

共 44 条

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