Diagenode

UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs.


Gozdecka M, Meduri E, Mazan M, Tzelepis K, Dudek M, Knights AJ, Pardo M, Yu L, Choudhary JS, Metzakopian E, Iyer V, Yun H, Park N, Varela I, Bautista R, Collord G, Dovey O, Garyfallos DA, De Braekeleer E, Kondo S, Cooper J, Göttgens B, Bullinger L, Northc

The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss. By integrating proteomic and genomic analyses, we link these changes to UTX regulation of ATP-dependent chromatin remodeling, coordination of the COMPASS complex and enhanced pioneering activity of ETS factors during evolution to AML. Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs.

Tags
Antibody

Share this article

Published
June, 2018

Source

Products used in this publication

  • cut and tag antibody icon
    C15410196
    H3K27ac polyclonal antibody
  • cut and tag antibody icon
    C15410194
    H3K4me1 polyclonal antibody
  • ChIP kit icon
    C01010051
    iDeal ChIP-seq kit for Histones
  • ChIP kit icon
    C01010055
    iDeal ChIP-seq kit for Transcription Factors

イベント

  • Virtual ChIP workshop - January 18-19, 2022 or January 25-26, 2022
    Diagenode
    Jan 18-Jan 26, 2022
  • Virtual DNA Methylation - January 18-19, 2022 or January 25-26, 2022
    Diagenode
    Jan 18-Jan 26, 2022
  • Lausanne Genomics Days 2022
    Lausanne, Switzerland
    Feb 14-Feb 15, 2022
 すべてのイベントを見る

ニュース

 すべてのニュースを見る


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


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