The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation.

The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation. Research Abstract Details 

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The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation. Abstract Text:

Kevin W McCool,Xiaojie Xu,Don B Singer,Fern E Murdoch,Michael K Fritsch,

We have examined the role of histone acetylation in the very earliest steps of differentiation of mouse embryonic stem cells in response to withdrawal of leukemia inhibitory factor (LIF) as a differentiation signal. The cells undergo dramatic changes in morphology and an ordered program of gene expression changes representing differentiation to all three germ layers over the first 3-5 days of LIF withdrawal. We observed a global increase in acetylation on histone H4 and to a lesser extent on histone H3 over this time period. Treatment of the cells with trichostatin A (TSA), a histone deacetylase inhibitor, induced changes in morphology, gene expression, and histone acetylation that mimicked differentiation induced by withdrawal of LIF. We examined localized histone acetylation in the regulatory regions of genes that were transcriptionally either active in undifferentiated cells, induced during differentiation, or inactive under all treatments. There was striking concordance in the histone acetylation patterns of specific genes induced by both TSA and LIF withdrawal. Increased histone acetylation in local regions correlated best with induction of gene expression. Finally, TSA treatment did not support the maintenance or progression of differentiation. Upon removal of TSA, the cells reverted to the undifferentiated phenotype. We concluded that increased histone acetylation at specific genes played a role in their expression, but additional events are required for maintenance of differentiated gene expression and loss of the pluripotent state.

The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation. Publishing Authors By Initials

KW McCool,X Xu,DB Singer,FE Murdoch,MK Fritsch,

For similar cells: stem cells: pluripotent stem cells research abstracts see: cells: stem cells: pluripotent stem cells research

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The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 6696-706

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 4

MONTH: 01

YEAR: 2007

The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation. Keywords Mesh Terms:

KEYWORDS: Pluripotent Stem Cells

MESH TERMS: physiology

Chemical & Substance for Abstract: The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation. Information

Substance Name: trichostatin A

Registry Number: 58880-19-6

Grant and Affiliation Information for The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation.

AFFILIATION: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R01DK64243

ACRONYM: DK

MEDLINETA: J Biol Chem

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