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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dawson, Mark A. Mann, Matthias Owen-hughes, Tom Gout, Ivan Olsen, Jesper V. Bannister, Andrew J. Somers, Joanna Hurd, Paul J. Halls, Karen Vermeulen, Michiel Ismail, Heba Kouzarides, Tony |
| Description | Author Affiliation: Hurd PJ ( Wellcome Trust and Cancer Research UK, Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom.) |
| Abstract | Numerous post-translational modifications have been identified in histones. Most of these occur within the histone tails, but a few have been identified within the histone core sequences. Histone core post-translational modifications have the potential to directly modulate nucleosome structure and consequently DNA accessibility. Here, we identify threonine 45 of histone H3 (H3T45) as a site of phosphorylation in vivo. We find that phosphorylation of H3T45 (H3T45ph) increases dramatically in apoptotic cells, around the time of DNA nicking. To further explore this connection, we analyzed human neutrophil cells because they are short-lived cells that undergo apoptosis in vivo. Freshly isolated neutrophils contain very little H3T45ph, whereas cells cultured for 20 h possess significant amounts; the kinetics of H3T45ph induction closely parallel those of caspase-3 activation. Cytokine inhibition of neutrophil apoptosis leads to reduced levels of H3T45ph. We identify protein kinase C-delta as the kinase responsible for H3T45ph in vitro and in vivo. Given the nucleosomal position of H3T45, we postulate that H3T45ph induces structural change within the nucleosome to facilitate DNA nicking and/or fragmentation. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 24 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-06-12 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Physiology Histones Metabolism Neutrophils Cytology Cell Differentiation HL-60 Cells Chemistry Nucleosomes Phosphorylation Protein Conformation Protein Kinase C-delta Threonine Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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