Histone H3 Lysine 56 Acetylation Is Linked to the Core Transcriptional Network in Human Embryonic Stem Cells

Wei Xie; Chunying Song; Nicolas L. Young; Adam S. Sperling; Feng Xu; Rupa Sridharan; Anne E. Conway; Benjamin A. Garcia; Kathrin Plath; Amander T. Clark; Michael Grunstein

doi:10.1016/j.molcel.2009.02.004

Histone H3 Lysine 56 Acetylation Is Linked to the Core Transcriptional Network in Human Embryonic Stem Cells

Wei Xie, Chunying Song, Nicolas L. Young, Adam S. Sperling, Feng Xu, Rupa Sridharan, Anne E. Conway, Benjamin A. Garcia, Kathrin Plath, Amander T. Clark, Michael Grunstein

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174 Scopus citations

Abstract

Lysine 56 acetylation in the helical core of histone H3 opens yeast chromatin and enables histone gene transcription, DNA replication, and DNA repair and prevents epigenetic silencing. While K56Ac is globally abundant in yeast and flies, its presence has been uncertain in mammals. We show here using mass spectrometry and genome-wide analyses that K56Ac is present in human embryonic stem cells (hESCs), overlapping strongly at active and inactive promoters with the binding of the key regulators of pluripotency, NANOG, SOX2, and OCT4. This includes also the canonical histone gene promoters and those for the hESC-specific microRNAs. K56Ac then relocates to developmental genes upon cellular differentiation. Thus the K56Ac state more accurately reflects the epigenetic differences between hESCs and somatic cells than other active histone marks such as H3 K4 trimethylation and K9 acetylation. These results suggest that K56Ac is involved in the human core transcriptional network of pluripotency.

Original language	English
Pages (from-to)	417-427
Number of pages	11
Journal	Molecular cell
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2009.02.004
State	Published - Feb 27 2009

Keywords

DNA
STEMCELL

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10.1016/j.molcel.2009.02.004

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title = "Histone H3 Lysine 56 Acetylation Is Linked to the Core Transcriptional Network in Human Embryonic Stem Cells",

abstract = "Lysine 56 acetylation in the helical core of histone H3 opens yeast chromatin and enables histone gene transcription, DNA replication, and DNA repair and prevents epigenetic silencing. While K56Ac is globally abundant in yeast and flies, its presence has been uncertain in mammals. We show here using mass spectrometry and genome-wide analyses that K56Ac is present in human embryonic stem cells (hESCs), overlapping strongly at active and inactive promoters with the binding of the key regulators of pluripotency, NANOG, SOX2, and OCT4. This includes also the canonical histone gene promoters and those for the hESC-specific microRNAs. K56Ac then relocates to developmental genes upon cellular differentiation. Thus the K56Ac state more accurately reflects the epigenetic differences between hESCs and somatic cells than other active histone marks such as H3 K4 trimethylation and K9 acetylation. These results suggest that K56Ac is involved in the human core transcriptional network of pluripotency.",

keywords = "DNA, STEMCELL",

author = "Wei Xie and Chunying Song and Young, {Nicolas L.} and Sperling, {Adam S.} and Feng Xu and Rupa Sridharan and Conway, {Anne E.} and Garcia, {Benjamin A.} and Kathrin Plath and Clark, {Amander T.} and Michael Grunstein",

note = "Funding Information: We are grateful to members of the Grunstein laboratory for generous help throughout this work. We thank Arnold Berk and Jennifer Woo for the gifts of HeLa and HEK293 cell lines; the UCLA microarray core facility for array services; and Siavash Kurdistani, Roberto Ferrari, Sheng Yin, and Wei Sun for discussions and advice. This work was supported by National Institutes of Health grants (to M.G.). A.T.C. is the recipient of a STOP CANCER career development award. K.P. is a Kimmel Scholar and is supported by the Margaret E. Early Trust Foundation. ",

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T1 - Histone H3 Lysine 56 Acetylation Is Linked to the Core Transcriptional Network in Human Embryonic Stem Cells

AU - Xie, Wei

AU - Song, Chunying

AU - Young, Nicolas L.

AU - Sperling, Adam S.

AU - Xu, Feng

AU - Sridharan, Rupa

AU - Conway, Anne E.

AU - Garcia, Benjamin A.

AU - Plath, Kathrin

AU - Clark, Amander T.

AU - Grunstein, Michael

N1 - Funding Information: We are grateful to members of the Grunstein laboratory for generous help throughout this work. We thank Arnold Berk and Jennifer Woo for the gifts of HeLa and HEK293 cell lines; the UCLA microarray core facility for array services; and Siavash Kurdistani, Roberto Ferrari, Sheng Yin, and Wei Sun for discussions and advice. This work was supported by National Institutes of Health grants (to M.G.). A.T.C. is the recipient of a STOP CANCER career development award. K.P. is a Kimmel Scholar and is supported by the Margaret E. Early Trust Foundation.

PY - 2009/2/27

Y1 - 2009/2/27

N2 - Lysine 56 acetylation in the helical core of histone H3 opens yeast chromatin and enables histone gene transcription, DNA replication, and DNA repair and prevents epigenetic silencing. While K56Ac is globally abundant in yeast and flies, its presence has been uncertain in mammals. We show here using mass spectrometry and genome-wide analyses that K56Ac is present in human embryonic stem cells (hESCs), overlapping strongly at active and inactive promoters with the binding of the key regulators of pluripotency, NANOG, SOX2, and OCT4. This includes also the canonical histone gene promoters and those for the hESC-specific microRNAs. K56Ac then relocates to developmental genes upon cellular differentiation. Thus the K56Ac state more accurately reflects the epigenetic differences between hESCs and somatic cells than other active histone marks such as H3 K4 trimethylation and K9 acetylation. These results suggest that K56Ac is involved in the human core transcriptional network of pluripotency.

AB - Lysine 56 acetylation in the helical core of histone H3 opens yeast chromatin and enables histone gene transcription, DNA replication, and DNA repair and prevents epigenetic silencing. While K56Ac is globally abundant in yeast and flies, its presence has been uncertain in mammals. We show here using mass spectrometry and genome-wide analyses that K56Ac is present in human embryonic stem cells (hESCs), overlapping strongly at active and inactive promoters with the binding of the key regulators of pluripotency, NANOG, SOX2, and OCT4. This includes also the canonical histone gene promoters and those for the hESC-specific microRNAs. K56Ac then relocates to developmental genes upon cellular differentiation. Thus the K56Ac state more accurately reflects the epigenetic differences between hESCs and somatic cells than other active histone marks such as H3 K4 trimethylation and K9 acetylation. These results suggest that K56Ac is involved in the human core transcriptional network of pluripotency.

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Histone H3 Lysine 56 Acetylation Is Linked to the Core Transcriptional Network in Human Embryonic Stem Cells

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