Epigenetic silencing of the oncogenic miR-17-92 cluster during PU.1-directed macrophage differentiation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F11%3A8965" target="_blank" >RIV/00216208:11110/11:8965 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/11:8965

Result on the web

<a href="http://dx.doi.org/10.1038/emboj.2011.317" target="_blank" >http://dx.doi.org/10.1038/emboj.2011.317</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Epigenetic silencing of the oncogenic miR-17-92 cluster during PU.1-directed macrophage differentiation

Original language description

The oncogenic cluster miR-17-92 encodes seven related microRNAs that regulate cell proliferation, apoptosis and development. Expression of miR-17-92 cluster is decreased upon cell differentiation. Here, we report a novel mechanism of the regulation of miR-17-92 cluster. Using transgenic PU.1(-/-) myeloid progenitors we show that upon macrophage differentiation, the transcription factor PU.1 induces the secondary determinant Egr2 which, in turn, directly represses miR-17-92 expression by recruiting histone demethylase Jarid1b leading to histone H3 lysine K4 demethylation within the CpG island at the miR-17-92 promoter. Conversely, Egr2 itself is targeted by miR-17-92, indicating existence of mutual regulatory relationship between miR-17-92 and Egr2. Furthermore, restoring EGR2 levels in primary acute myeloid leukaemia blasts expressing elevated levels of miR-17-92 and low levels of PU.1 and EGR2 leads to downregulation of miR-17-92 and restored expression of its targets p21CIP1 and BIM.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2011

Confidentiality

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

Name of the periodical

EMBO Journal

ISSN

0261-4189

e-ISSN

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Volume of the periodical

30

Issue of the periodical within the volume

21

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

4450-4464

UT code for WoS article

000296716600012

EID of the result in the Scopus database

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