CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression

Su Hyung Park; Seung Eun Yu; Young Gyu Chai; Yeun Kyu Jang

doi:10.1093/nar/gku263

CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression

Su Hyung Park, Seung Eun Yu, Young Gyu Chai, Yeun Kyu Jang

Department of Systems Biology

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

Although several studies have suggested that the functions of heterochromatin regulators may be regulated by post-translational modifications during cell cycle progression, regulation of the histone methyltransferase Suv39H1 is not fully understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391 and these phosphorylation levels oscillate during the cell cycle, peaking at S phase and maintained during S-G2-M phase. The CDK2-mediated phosphorylation of Suv39H1 at Ser391 results in preferential dissociation from chromatin. Furthermore, phosphorylation-mediated dissociation of Suv39H1 from chromatin causes an enhanced occupancy of JMJD2A histone demethylase on heterochromatin and alterations in inactive histone marks. Overexpression of phospho-mimic Suv39H1 induces early replication of heterochromatin, suggesting the importance of Suv39H1 phosphorylation in the replication of heterochromatin. Moreover, overexpression of phospho-defective Suv39H1 caused altered replication timing of heterochromatin and increases sensitivity to replication stress. Collectively, our data suggest that phosphorylation-mediated modulation of Suv39H1-chromatin association may be an initial step in heterochromatin replication.

Original language	English
Pages (from-to)	6196-6207
Number of pages	12
Journal	Nucleic acids research
Volume	42
Issue number	10
DOIs	https://doi.org/10.1093/nar/gku263
Publication status	Published - 2014 Jun 2

Bibliographical note

Funding Information:
National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) [2011-0030049, in part]; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [0920260]; Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology [2010-0010639]; NRF Grant funded by the Korean Government [2009-0075197]; Mid-career Researcher Program through NRF grant funded by the MEST [2009-0083772, in part]; Yonsei University Research Fund [2013-12-0087, in part, to S.H.P]; Brain Korea21Plus (BK21+) Program (S.H.P., S.E.Y. and Y.K.J.). Source of open access funding: NRF grant funded by the Korea government (MSIP) [2011-0030049]. Conflict of interest statement. None declared.

All Science Journal Classification (ASJC) codes

Genetics

Access to Document

10.1093/nar/gku263

Cite this

@article{3ba170ffa31e46c9a263c767cf891ad4,

title = "CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression",

abstract = "Although several studies have suggested that the functions of heterochromatin regulators may be regulated by post-translational modifications during cell cycle progression, regulation of the histone methyltransferase Suv39H1 is not fully understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391 and these phosphorylation levels oscillate during the cell cycle, peaking at S phase and maintained during S-G2-M phase. The CDK2-mediated phosphorylation of Suv39H1 at Ser391 results in preferential dissociation from chromatin. Furthermore, phosphorylation-mediated dissociation of Suv39H1 from chromatin causes an enhanced occupancy of JMJD2A histone demethylase on heterochromatin and alterations in inactive histone marks. Overexpression of phospho-mimic Suv39H1 induces early replication of heterochromatin, suggesting the importance of Suv39H1 phosphorylation in the replication of heterochromatin. Moreover, overexpression of phospho-defective Suv39H1 caused altered replication timing of heterochromatin and increases sensitivity to replication stress. Collectively, our data suggest that phosphorylation-mediated modulation of Suv39H1-chromatin association may be an initial step in heterochromatin replication.",

author = "Park, {Su Hyung} and Yu, {Seung Eun} and Chai, {Young Gyu} and Jang, {Yeun Kyu}",

note = "Funding Information: National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) [2011-0030049, in part]; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [0920260]; Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology [2010-0010639]; NRF Grant funded by the Korean Government [2009-0075197]; Mid-career Researcher Program through NRF grant funded by the MEST [2009-0083772, in part]; Yonsei University Research Fund [2013-12-0087, in part, to S.H.P]; Brain Korea21Plus (BK21+) Program (S.H.P., S.E.Y. and Y.K.J.). Source of open access funding: NRF grant funded by the Korea government (MSIP) [2011-0030049]. Conflict of interest statement. None declared.",

year = "2014",

month = jun,

day = "2",

doi = "10.1093/nar/gku263",

language = "English",

volume = "42",

pages = "6196--6207",

journal = "Nucleic acids research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "10",

}

TY - JOUR

T1 - CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression

AU - Park, Su Hyung

AU - Yu, Seung Eun

AU - Chai, Young Gyu

AU - Jang, Yeun Kyu

N1 - Funding Information: National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) [2011-0030049, in part]; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [0920260]; Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology [2010-0010639]; NRF Grant funded by the Korean Government [2009-0075197]; Mid-career Researcher Program through NRF grant funded by the MEST [2009-0083772, in part]; Yonsei University Research Fund [2013-12-0087, in part, to S.H.P]; Brain Korea21Plus (BK21+) Program (S.H.P., S.E.Y. and Y.K.J.). Source of open access funding: NRF grant funded by the Korea government (MSIP) [2011-0030049]. Conflict of interest statement. None declared.

PY - 2014/6/2

Y1 - 2014/6/2

N2 - Although several studies have suggested that the functions of heterochromatin regulators may be regulated by post-translational modifications during cell cycle progression, regulation of the histone methyltransferase Suv39H1 is not fully understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391 and these phosphorylation levels oscillate during the cell cycle, peaking at S phase and maintained during S-G2-M phase. The CDK2-mediated phosphorylation of Suv39H1 at Ser391 results in preferential dissociation from chromatin. Furthermore, phosphorylation-mediated dissociation of Suv39H1 from chromatin causes an enhanced occupancy of JMJD2A histone demethylase on heterochromatin and alterations in inactive histone marks. Overexpression of phospho-mimic Suv39H1 induces early replication of heterochromatin, suggesting the importance of Suv39H1 phosphorylation in the replication of heterochromatin. Moreover, overexpression of phospho-defective Suv39H1 caused altered replication timing of heterochromatin and increases sensitivity to replication stress. Collectively, our data suggest that phosphorylation-mediated modulation of Suv39H1-chromatin association may be an initial step in heterochromatin replication.

AB - Although several studies have suggested that the functions of heterochromatin regulators may be regulated by post-translational modifications during cell cycle progression, regulation of the histone methyltransferase Suv39H1 is not fully understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391 and these phosphorylation levels oscillate during the cell cycle, peaking at S phase and maintained during S-G2-M phase. The CDK2-mediated phosphorylation of Suv39H1 at Ser391 results in preferential dissociation from chromatin. Furthermore, phosphorylation-mediated dissociation of Suv39H1 from chromatin causes an enhanced occupancy of JMJD2A histone demethylase on heterochromatin and alterations in inactive histone marks. Overexpression of phospho-mimic Suv39H1 induces early replication of heterochromatin, suggesting the importance of Suv39H1 phosphorylation in the replication of heterochromatin. Moreover, overexpression of phospho-defective Suv39H1 caused altered replication timing of heterochromatin and increases sensitivity to replication stress. Collectively, our data suggest that phosphorylation-mediated modulation of Suv39H1-chromatin association may be an initial step in heterochromatin replication.

UR - http://www.scopus.com/inward/record.url?scp=84903184595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903184595&partnerID=8YFLogxK

U2 - 10.1093/nar/gku263

DO - 10.1093/nar/gku263

M3 - Article

C2 - 24728993

AN - SCOPUS:84903184595

SN - 0305-1048

VL - 42

SP - 6196

EP - 6207

JO - Nucleic acids research

JF - Nucleic acids research

IS - 10

ER -

CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this