Diagenode

KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress.


Lezina L, Aksenova V, Ivanova T, Purmessur N, Antonov AV, Tentler D, Fedorova O, Garabadgiu AV, Talianidis I, Melino G, Barlev NA

During the recent years lysine methyltransferase Set7/9 ((Su(var)-3-9, Enhancer-of-Zeste, Trithorax) domain containing protein 7/9) has emerged as an important regulator of different transcription factors. In this study, we report a novel function for Set7/9 as a critical co-activator of E2 promoter-binding factor 1 (E2F1)-dependent transcription in response to DNA damage. By means of various biochemical, cell biology, and bioinformatics approaches, we uncovered that cell-cycle progression through the G1/S checkpoint of tumour cells upon DNA damage is defined by the threshold of expression of both E2F1 and Set7/9. The latter affects the activity of E2F1 by indirectly modulating histone modifications in the promoters of E2F1-dependent genes. Moreover, Set7/9 differentially affects E2F1 transcription targets: it promotes cell proliferation via expression of the CCNE1 gene and represses apoptosis by inhibiting the TP73 gene. Our biochemical screening of the panel of lung tumour cell lines suggests that these two factors are critically important for transcriptional upregulation of the CCNE1 gene product and hence successful progression through cell cycle. These findings identify Set7/9 as a potential biomarker in tumour cells with overexpressed E2F1 activity.Cell Death and Differentiation advance online publication, 15 August 2014; doi:10.1038/cdd.2014.108.

Tags
Bioruptor
Chromatin Shearing
ChIP-qPCR
Antibody

Share this article

Published
August, 2014

Source

Products used in this publication

  • Antibody ChIP-seq grade icon
    C15410056
    H3K9me3 polyclonal antibody

イベント

  • ASHG
    Houston, TX
    Oct 15-Oct 19, 2019
  • ddd
    dd
    Oct 18-Oct 26, 2019
  • Neuroscience 2019
    Chicago, IL
    Oct 19-Oct 23, 2019
 すべてのイベントを見る

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics