CDK11 is required for transcription of replication-dependent histone genes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00113910" target="_blank" >RIV/00216224:14740/20:00113910 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D" target="_blank" >https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41594-020-0406-8" target="_blank" >10.1038/s41594-020-0406-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

CDK11 is required for transcription of replication-dependent histone genes

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

CDK11 is required for transcription of replication-dependent histone genes

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA16-10930S" target="_blank" >GA16-10930S: Regulace genové exprese novým faktorem vázajícím mRNA</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

NATURE STRUCTURAL & MOLECULAR BIOLOGY

ISSN

1545-9993

e-ISSN

1545-9985

Svazek periodika

27

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

500-510

Kód UT WoS článku

000530278100003

EID výsledku v databázi Scopus

2-s2.0-85084508015