CDK11 is required for transcription of replication-dependent
histone genes

J 2020

CDK11 is required for transcription of replication-dependent histone genes

GAJDUŠKOVÁ, Pavla, I.R. DE LOS MOZOS, Michal RÁJECKÝ, Milan HLUCHÝ, J. ULE et. al.

Basic information

Original name

CDK11 is required for transcription of replication-dependent histone genes

Authors

GAJDUŠKOVÁ, Pavla (203 Czech Republic, belonging to the institution), I.R. DE LOS MOZOS, Michal RÁJECKÝ (203 Czech Republic, belonging to the institution), Milan HLUCHÝ (703 Slovakia, belonging to the institution), J. ULE and Dalibor BLAŽEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2020, 1545-9993

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 15.369

RIV identification code

RIV/00216224:14740/20:00113910

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1038/s41594-020-0406-8

UT WoS

000530278100003

Keywords in English

RNA-POLYMERASE-II; TERMINAL DOMAIN; CELL-GROWTH; IN-VIVO; CTD; EXPRESSION; PROMOTES; IDENTIFICATION; THREONINE-4; COMPLEXES

Abstract

V originále

CDK11 functions with histone pre-mRNA-processing factor FLASH to upregulate expression of replication-dependent histone genes in S phase and to couple transcription and processing of nascent histone transcripts in mammalian cells. Replication-dependent histones (RDH) are required for packaging of newly synthetized DNA into nucleosomes during the S phase when their expression is highly upregulated. However, the mechanisms of this upregulation in metazoan cells remain poorly understood. Using iCLIP and ChIP-seq, we found that human cyclin-dependent kinase 11 (CDK11) associates with RNA and chromatin of RDH genes primarily in the S phase. Moreover, its amino-terminal region binds FLASH, an RDH-specific 3 '-end processing factor, which keeps the kinase on the chromatin. CDK11 phosphorylates serine 2 (Ser2) of the carboxy-terminal domain of RNA polymerase II (RNAPII), which is initiated when RNAPII reaches the middle of RDH genes and is required for further RNAPII elongation and 3 '-end processing. CDK11 depletion leads to decreased number of cells in S phase, likely owing to the function of CDK11 in RDH gene expression. Thus, the reliance of RDH expression on CDK11 could explain why CDK11 is essential for the growth of many cancers.

Links

CZ.1.05/1.1.00/02.0068, interní kód MU

Name: CEITEC - středoevropský technologický institut (Acronym: CEITEC)

Investor: Ministry of Education, Youth and Sports of the CR, CEITEC - Central European Institute of Technology, 1.1 European Centres of Excellence

GA16-10930S, research and development project

Name: Regulace genové exprese novým faktorem vázajícím mRNA

Investor: Czech Science Foundation

MUNI/E/0080/2017, interní kód MU

Name: Genome-wide analyses of a “non-canonical” cyclin-dependent kinase (CDK)

Investor: Masaryk University, Promoting quality excellence

MUNI/E/0990/2018, interní kód MU

Name: Charakterization of a new factor in regulation of transcription/mRNA processing of histone genes

Investor: Masaryk University, Promoting quality excellence

Citovat

GAJDUŠKOVÁ, Pavla, I.R. DE LOS MOZOS, Michal RÁJECKÝ, Milan HLUCHÝ, J. ULE and Dalibor BLAŽEK. CDK11 is required for transcription of replication-dependent histone genes. NATURE STRUCTURAL & MOLECULAR BIOLOGY. 2020, vol. 27, No 5, p. 500-510, 33 pp. ISSN 1545-9993. Available from: https://dx.doi.org/10.1038/s41594-020-0406-8.

@article{1652296,
   author = {Gajdušková, Pavla and de los Mozos, I.R. and Rájecký, Michal and Hluchý, Milan and Ule, J. and Blažek, Dalibor},
   article_number = {5},
   doi = {http://dx.doi.org/10.1038/s41594-020-0406-8},
   keywords = {RNA-POLYMERASE-II; TERMINAL DOMAIN; CELL-GROWTH; IN-VIVO; CTD; EXPRESSION; PROMOTES; IDENTIFICATION; THREONINE-4; COMPLEXES},
   language = {eng},
   issn = {1545-9993},
   journal = {NATURE STRUCTURAL & MOLECULAR BIOLOGY},
   title = {CDK11 is required for transcription of replication-dependent histone genes},
   url = {https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D},
   volume = {27},
   year = {2020}
}

TY  - JOUR
ID  - 1652296
AU  - Gajdušková, Pavla - de los Mozos, I.R. - Rájecký, Michal - Hluchý, Milan - Ule, J. - Blažek, Dalibor
PY  - 2020
TI  - CDK11 is required for transcription of replication-dependent histone genes
JF  - NATURE STRUCTURAL & MOLECULAR BIOLOGY
VL  - 27
IS  - 5
SP  - 500-510
EP  - 500-510
SN  - 15459993
KW  - RNA-POLYMERASE-II
KW  - TERMINAL DOMAIN
KW  - CELL-GROWTH
KW  - IN-VIVO
KW  - CTD
KW  - EXPRESSION
KW  - PROMOTES
KW  - IDENTIFICATION
KW  - THREONINE-4
KW  - COMPLEXES
UR  - https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D
L2  - https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D
N2  - CDK11 functions with histone pre-mRNA-processing factor FLASH to upregulate expression of replication-dependent histone genes in S phase and to couple transcription and processing of nascent histone transcripts in mammalian cells. Replication-dependent histones (RDH) are required for packaging of newly synthetized DNA into nucleosomes during the S phase when their expression is highly upregulated. However, the mechanisms of this upregulation in metazoan cells remain poorly understood. Using iCLIP and ChIP-seq, we found that human cyclin-dependent kinase 11 (CDK11) associates with RNA and chromatin of RDH genes primarily in the S phase. Moreover, its amino-terminal region binds FLASH, an RDH-specific 3 '-end processing factor, which keeps the kinase on the chromatin. CDK11 phosphorylates serine 2 (Ser2) of the carboxy-terminal domain of RNA polymerase II (RNAPII), which is initiated when RNAPII reaches the middle of RDH genes and is required for further RNAPII elongation and 3 '-end processing. CDK11 depletion leads to decreased number of cells in S phase, likely owing to the function of CDK11 in RDH gene expression. Thus, the reliance of RDH expression on CDK11 could explain why CDK11 is essential for the growth of many cancers.
ER  -

GAJDUŠKOVÁ, Pavla, I.R. DE LOS MOZOS, Michal RÁJECKÝ, Milan HLUCHÝ, J. ULE and Dalibor BLAŽEK. CDK11 is required for transcription of replication-dependent histone genes. \textit{NATURE STRUCTURAL \&{} MOLECULAR BIOLOGY}. 2020, vol.~27, No~5, p.~500-510, 33 pp. ISSN~1545-9993. Available from: https://dx.doi.org/10.1038/s41594-020-0406-8.

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