Phosphorylation of histone H3 Thr-45 is linked to apoptosis
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Phosphorylation of histone H3 Thr-45 is linked to apoptosis. / Hurd, Paul J; Bannister, Andrew J; Halls, Karen; Dawson, Mark A; Vermeulen, Michiel; Olsen, Jesper V; Ismail, Heba; Somers, Joanna; Mann, Matthias; Owen-Hughes, Tom; Gout, Ivan; Kouzarides, Tony.
In: Journal of Biological Chemistry, Vol. 284, No. 24, 2009, p. 16575-83.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Phosphorylation of histone H3 Thr-45 is linked to apoptosis
AU - Hurd, Paul J
AU - Bannister, Andrew J
AU - Halls, Karen
AU - Dawson, Mark A
AU - Vermeulen, Michiel
AU - Olsen, Jesper V
AU - Ismail, Heba
AU - Somers, Joanna
AU - Mann, Matthias
AU - Owen-Hughes, Tom
AU - Gout, Ivan
AU - Kouzarides, Tony
N1 - Keywords: Apoptosis; Cell Differentiation; HL-60 Cells; Histones; Humans; Neutrophils; Nucleosomes; Phosphorylation; Protein Conformation; Protein Kinase C-delta; Threonine
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M109.005421
DO - 10.1074/jbc.M109.005421
M3 - Journal article
C2 - 19363025
VL - 284
SP - 16575
EP - 16583
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 24
ER -
ID: 14701330