Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells
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- Shereen Jamaladdin
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- Richard D. W. Kelly
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- Laura O’Regan
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- Oliver M. Dovey
- Wellcome Trust Sanger Institute, Hinxton, Cambs CB10 1SA, United Kingdom
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- Grace E. Hodson
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- Christopher J. Millard
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- Nicola Portolano
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- Andrew M. Fry
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- John W. R. Schwabe
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
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- Shaun M. Cowley
- Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom; and
説明
<jats:title>Significance</jats:title> <jats:p> Histone deacetylase 1 and 2 (HDAC1/2) are sister proteins that regulate access to DNA by modulating chromatin. We have generated the first double knockout (DKO) of <jats:italic>Hdac1/2</jats:italic> in embryonic stem (ES) cells and find that gene inactivation causes a loss of cell viability, which is associated with increased abnormal mitotic spindles and chromosome segregation defects. Transcriptome analysis revealed that almost 2,000 genes are deregulated in DKO cells. Significantly for the self-renewal properties of ES cells, this includes down-regulation of the core pluripotent factors, Oct4, Nanog, and Rex1. Furthermore, using the rescue of <jats:italic>Hdac1/2</jats:italic> -null cells as a model system to monitor HDAC1/2 activity, we have also shown that mutations that abolish inositol tetraphosphate binding reduce the activity of HDAC1 in vivo. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 111 (27), 9840-9845, 2014-06-23
Proceedings of the National Academy of Sciences