Mitotic phosphorylation of histone H3 at threonine 3

Polioudaki, Hara; Markaki, Yolanda; Kourmouli, Niki; Dialynas, George; Theodoropoulos, Panayiotis A.; Singh, Prim B.; Georgatos, Spyros D.

doi:10.1016/s0014-5793(04)00060-2

Cited by 104 publications

(123 citation statements)

References 43 publications

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“…Thr-3 is an evolutionarily conserved residue in histone H3, but the specific function of its phosphorylated form is unclear and may differ between animals and plants. In mammals, H3T3ph is abundant in mitotic chromosome centromeres but virtually undetectable in interphase cells (11,29). Moreover, phosphorylation of H3T3 by the kinase Haspin (unrelated to MUT9p) has been implicated in sister chromatid cohesion and chromosome segregation (11).…”

Section: Discussionmentioning

confidence: 99%

The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas

Casas-Mollano¹,

Jeong²,

Xu³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

101

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Section: Discussionmentioning

confidence: 99%

The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas

Casas-Mollano¹,

Jeong²,

Xu³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

101

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“…The phosphorylation of histone H3 at Thr 3, mainly in mitotic cells, has been recently characterized in a number of organisms (12,13,15,16,(21)(22)(23). In mammals, H3T3ph is more prevalent in the centromeric region of metaphase chromosomes and has been implicated in chromosome alignment and centromeric cohesion (12,13,16).…”

mentioning

confidence: 99%

Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana

Wang

Casas-Mollano

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

132

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Histone phosphorylation plays key roles in stress-induced transcriptional reprogramming in metazoans but its function(s) in land plants has remained relatively unexplored. Here we report that an Arabidopsis mutant defective in At3g03940 and At5g18190, encoding closely related Ser/Thr protein kinases, shows pleiotropic phenotypes including dwarfism and hypersensitivity to osmotic/salt stress. The double mutant has reduced global levels of phosphorylated histone H3 threonine 3 (H3T3ph), which are not enhanced, unlike the response in the wild type, by drought-like treatments. Genome-wide analyses revealed increased H3T3ph, slight enhancement in trimethylated histone H3 lysine 4 (H3K4me3), and a modest decrease in histone H3 occupancy in pericentromeric/knob regions of wild-type plants under osmotic stress. However, despite these changes in heterochromatin, transposons and repeats remained transcriptionally repressed. In contrast, this reorganization of heterochromatin was mostly absent in the double mutant, which exhibited lower H3T3ph levels in pericentromeric regions even under normal environmental conditions. Interestingly, within actively transcribed protein-coding genes, H3T3ph density was minimal in 5′ genic regions, coincidental with a peak of H3K4me3 accumulation. This pattern was not affected in the double mutant, implying the existence of additional H3T3 protein kinases in Arabidopsis. Our results suggest that At3g03940 and At5g18190 are involved in the phosphorylation of H3T3 in pericentromeric/knob regions and that this repressive epigenetic mark may be important for maintaining proper heterochromatic organization and, possibly, chromosome function(s).epigenetics | heterochromatin | histone phosphorylation | abiotic stress | protein kinase

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“…H3T3 phosphorylation occurs specifically during mitosis and is particularly prominent at inner centromere regions (6,7,9). Recently, H3T3ph has been suggested to relieve an inhibitory effect of histone H3 on Aurora B, leading to activation of this key mitotic kinase (10).…”

mentioning

confidence: 99%

Structure and functional characterization of the atypical human kinase haspin

Eswaran

Patnaik

Filippakopoulos

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

155

167

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The protein kinase haspin/Gsg2 plays an important role in mitosis, where it specifically phosphorylates Thr-3 in histone H3 (H3T3). Its protein sequence is only weakly homologous to other protein kinases and lacks the highly conserved motifs normally required for kinase activity. Here we report structures of human haspin in complex with ATP and the inhibitor iodotubercidin. These structures reveal a constitutively active kinase conformation, stabilized by haspin-specific inserts. Haspin also has a highly atypical activation segment well adapted for specific recognition of the basic histone tail. Despite the lack of a DFG motif, ATP binding to haspin is similar to that in classical kinases; however, the ATP ␥-phosphate forms hydrogen bonds with the conserved catalytic loop residues Asp-649 and His-651, and a His651Ala haspin mutant is inactive, suggesting a direct role for the catalytic loop in ATP recognition. Enzyme kinetic data show that haspin phosphorylates substrate peptides through a rapid equilibrium random mechanism. A detailed analysis of histone modifications in the neighborhood of H3T3 reveals that increasing methylation at Lys-4 (H3K4) strongly decreases substrate recognition, suggesting a key role of H3K4 methylation in the regulation of haspin activity.ATP binding ͉ histone modification ͉ phosphorylation mechanism ͉ germ cell-specific gene 2 (Gsg2) ͉ mitosis E ukaryotic protein kinases (ePKs) constitute a large group of enzymes that regulate a vast diversity of cellular processes. Kinase activity depends on a number of highly conserved sequence motifs required for ATP/Mg 2ϩ binding and catalysis. About 10% of human ePKs lack one or more essential catalytic motifs and have been initially classified as inactive pseudokinases (1). However, a number of such proteins are active kinases, including haspin [haploid germ cell-specific nuclear protein kinase, encoded by Germ cell-specific gene 2 (Gsg2)]. Haspin lacks both the conserved ATP/Mg 2ϩ binding motif Asp-Phe-Gly (DFG), which is replaced by Asp-Tyr-Thr (DYT), and the Ala-Pro-Glu (APE) motif usually found at the C terminus of the activation segment (2). In addition, haspin shares only weak sequence homology with ePKs and contains a highly divergent kinase domain with several unique inserts (2, 3). Haspin mRNA is abundant in testis and also present in somatic cells (4, 5), and orthologues are found throughout eukaryotic phyla (2). Ectopically expressed haspin localizes to the nucleus in interphase and to the chromosomes in mitosis (4, 6), while depletion of haspin leads to premature chromatid separation, failure of chromosome alignment, and a block in mitosis in a prometaphase-like state (6, 7).Haspin autophosphorylates in vitro (4, 6, 8) and phosphorylates its only currently known substrate, histone H3, at threonine-3 (H3T3ph) both in vitro and in cells (6). H3T3 phosphorylation occurs specifically during mitosis and is particularly prominent at inner centromere regions (6, 7, 9). Recently, H3T3ph has been suggested to relieve an inhibitory effect of ...

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Mitotic phosphorylation of histone H3 at threonine 3

Cited by 104 publications

References 43 publications

The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas

The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas

Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana

Structure and functional characterization of the atypical human kinase haspin

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