Protein Kinase A-Mediated Serine 35 Phosphorylation Dissociates Histone H1.4 from Mitotic Chromosome
Date Issued
2011
Date
2011
Author(s)
Chu, Chi-Shuen
Abstract
Global histone H1 phosphorylation correlates with cell cycle progression. However, the function of site-specific H1 variant phosphorylation remains unclear. Our mass spectrometry analysis revealed several new modifications on H1. Among them, a novel N-terminal phosphorylation of the major H1 variant H1.4 at serine 35 (H1.4S35ph) was found to accumulate at mitosis. Protein kinase A (PKA) was found to be a kinase for H1.4S35. Importantly, S35-phosphorylated H1.4 contains weaker binding affinity to mitotic chromatin. Moreover, H1.4S35A substitution mutant cannot efficiently rescue the mitotic defect following H1.4 depletion and inhibition of PKA activity increases the mitotic chromatin compaction depending on H1.4. In addition, an adjacent methylation on lysine 33 was also identified. We further demonstrated that SET7, a histone H3K4 methyltransferase, can methylate H1.4K33 both in vivo and in vitro. Finally, a crosstalk between H1.4S35ph and H1.4K33me was characterized. Our results not only indicate that PKA-mediated H1.4S35 phosphorylation interferes H1.4 binding affinity to mitotic chromatin, but also suggest that this phosphorylation is necessary for specific mitotic functions. Our data suggest that the adjacent H1.4K33me might be involved in this regulation.
Subjects
Linker histone
H1
H1.4
protein kinase A
cAMP-dependent protein kinase
PKA
Cell cycle
phosphorylation
mitosis
DNA compaction
Type
thesis
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