A histone code in meiosis: the histone kinase, NHK-1, is required for proper chromosomal architecture in <i>Drosophila</i> oocytes

Ivanovska, Irena L.; Khandan, Tulasi; Ito, Takashi; Orr‐Weaver, Terry L.

doi:10.1101/gad.1348905

Cited by 90 publications

(129 citation statements)

References 64 publications

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“…Inhibition of Ser10 phosphorylation by inactivating aurora B with hesperadin, an inhibitor, also leads to improper attachment of kinetochore fibers to the chromosome (24), changes in binding properties of chromatin proteins such as HP1 (7,17), and failure to recruit the condensin complex and mitotic spindle assembly (10). NHK-1, a Drosophila homolog of VRK1, phosphorylates T119 in histone H2A and plays an essential role in mitotic progression and in the formation of chromosome architecture in meiosis (1,4,19). Although the net level of phosphorylation of histone H2A by VRK1 was weaker than that seen with H3 during in vitro kinase assay (Fig.…”

Section: Discussionmentioning

confidence: 95%

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Mitotic Histone H3 Phosphorylation by Vaccinia-Related Kinase 1 in Mammalian Cells

Kang

Park

Choi

et al. 2007

Molecular and Cellular Biology

147

191

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Mitotic chromatin condensation is essential for cell division in eukaryotes. Posttranslational modification of the N-terminal tail of histone proteins, particularly by phosphorylation by mitotic histone kinases, may facilitate this process. In mammals, aurora B is believed to be the mitotic histone H3 Ser10 kinase; however, it is not sufficient to phosphorylate H3 Ser10 with aurora B alone. We show that histone H3 is phosphorylated by vaccinia-related kinase 1 (VRK1). Direct phosphorylation of Thr3 and Ser10 in H3 by VRK1 both in vitro and in vivo was observed. Loss of VRK1 activity was associated with a marked decrease in H3 phosphorylation during mitosis. Phosphorylation of Ser10 by VRK1 is similar to that by aurora B. Moreover, expression and chromatin localization of VRK1 depended on the cell cycle phase. Overexpression of VRK1 resulted in a dramatic condensation of nuclei. Our findings collectively support a role of VRK1 as a novel mitotic histone H3 kinase in mammals.Chromatin congregates to chromosomes during mitosis to facilitate the even segregation of genetic information to two daughter cells. In nucleosomes, the combinational modification of histone tails, the so-called "histone code," controls chromatintemplated processes from gene expression to cell fate decision (20,30). Phosphorylation of the N-terminal tail of histone H3 may be responsible for chromatin condensation (21). During mitosis, the N-terminal tail of histone H3 is phosphorylated at several residues, including Thr3 (5, 36), Ser10 (3,7,17,18), Thr11 (37), and Ser28 (12). A correlation between histone H3 Ser10 phosphorylation and chromatin condensation in Aspergillus nidulans (6) and Tetrahymena thermophila (47) is well established. However, in other species, condensation is not accomplished simply by Ser10 phosphorylation, and additional phosphorylation or modification of histone tails is required (21).A number of studies have shown that members of the aurora kinase family are responsible for phosphorylation of histone H3 (3,7,17,18). Mammals contain three isotypes of aurora kinase designated aurora A, B, and C (11). Among these, aurora B is a strong candidate phosphorylator of Ser10 in histone H3 as is evident from data obtained with hesperadin, the aurora B inhibitor (14), which suppressed Ser10 phosphorylation during mitosis (7, 17). However, residual Ser10 phosphorylation was detected, even upon depletion of aurora B in cells, suggesting the presence of an additional histone H3 kinase (29).NIMA (never in mitosis), the histone H3 Ser10 kinase in Aspergillus nidulans (6, 34), triggers chromatin condensation in cells arrested at the interphase (28). In mammals, Nercc1, the functional ortholog of NIMA, was found to be phosphorylating histone H3 (39). Nucleosomal histone kinase 1 (NHK1) from Drosophila melanogaster is the kinase shown to phosphorylate histone protein in chromatin as a substrate. NHK1 phosphorylated H2A at Thr119 in chromatin but not with free histone as the substrate (1). Recent studies showed that NHK1 participates in mit...

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Section: Discussionmentioning

confidence: 95%

“…NHK1 phosphorylated H2A at Thr119 in chromatin but not with free histone as the substrate (1). Recent studies showed that NHK1 participates in mitotic progression (4) and maintenance of proper chromosomal architecture (19). These data strongly indicate that NHK1 is a bona fide mitotic histone kinase.…”

mentioning

confidence: 97%

Mitotic Histone H3 Phosphorylation by Vaccinia-Related Kinase 1 in Mammalian Cells

Kang

Park

Choi

et al. 2007

Molecular and Cellular Biology

147

191

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show abstract

“…Later the unique Drosophila melanogaster ortholog of this human kinase family, the NHK-1 (nucleosomal histone kinase), has also been shown to phosphorylate histones and is essential for chromosome condensation and mitotic progression (47)(48)(49)(50). Histone H3 plays an important role in chromatin condensation once the DNA synthesis has 3 H]GDP followed by incubation with the specified amounts of RCC1 for 5 min and 2 mM GTP without VRK1 or with different amounts of VRK1.…”

Section: Discussionmentioning

confidence: 99%

Proteomics Identification of Nuclear Ran GTPase as an Inhibitor of Human VRK1 and VRK2 (Vaccinia-related Kinase) Activities

Sanz-García¹,

López-Sánchez²,

Lazo

2008

Molecular & Cellular Proteomics

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Human vaccinia-related kinase (VRK) 1 is a novel serinethreonine kinase that regulates several transcription factors, nuclear envelope assembly, and chromatin condensation and is also required for cell cycle progression. The regulation of this kinase family is unknown. Mass spectrometry has permitted the identification of Ran as an interacting and regulatory protein of the VRK serine-threonine kinase activities. The stable interaction has been validated by pulldown of endogenous proteins as well as by reciprocal immunoprecipitations. The three members of the VRK family stably interact with Ran, and the interaction was not affected by the bound nucleotide, GDP or GTP. The interaction was stronger with the RanT24N that is locked in its inactive conformation and cannot bind nucleotides. None of the kinases phosphorylated Ran or RCC1. VRK1 does not directly interact with RCC1, but if Ran is present they can be isolated as a complex. The main effect of the interaction of inactive RanGDP with VRK1 is the inhibition of its kinase activity, which was detected by a reduction in VRK1 autophosphorylation and a reduction in phosphorylation of histone H3 in residues Thr-3 and Ser-10. The kinase activity inhibition can be relieved by the interaction with the constitutively active RanGTP or RanL43E, which locks Ran in its GTP-bound active conformation. In this complex, the interaction with VRK proteins does not alter the effect of its guanine exchange factor, RCC1. Ran is a novel negative regulator of nuclear VRK1 and VRK2 kinase activity, which may vary in different subcellular localizations generating an asymmetric intracellular distribution of kinase activity depending on local protein interactions.

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“…Other less-well-understood candidates that may indeed be the phosphorylation relevant to condensation include H2ASer1ph, H2BSer10ph, H2ATur119ph and H4ph. [85][86][87][88] Histone modifications and chromosome segregation. Histone acetylation has been reported to be associated with chromosome segregation in oocyte meiosis.…”

Section: Functions Of Histone Modifications During Mammalian Oocyte Mmentioning

confidence: 99%

Histone modifications during mammalian oocyte maturation: Dynamics, regulation and functions

Gu¹,

Wang²,

Sun³

2010

Cell Cycle

124

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A histone code in meiosis: the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes

Cited by 90 publications

References 64 publications

Mitotic Histone H3 Phosphorylation by Vaccinia-Related Kinase 1 in Mammalian Cells

Mitotic Histone H3 Phosphorylation by Vaccinia-Related Kinase 1 in Mammalian Cells

Proteomics Identification of Nuclear Ran GTPase as an Inhibitor of Human VRK1 and VRK2 (Vaccinia-related Kinase) Activities

Histone modifications during mammalian oocyte maturation: Dynamics, regulation and functions

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