Diagenode

The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer.


Zhu Q, Fang L, Heuberger J, Kranz A, Schipper J, Scheckenbach K, Vidal RO, Sunaga-Franze DY, Müller M, Wulf-Goldenberg A, Sauer S, Birchmeier W

We identified a regulatory system that acts downstream of Wnt/β-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/β-catenin gain-of-function and Bmpr1a loss-of-function mutations that tumor-propagating cells exhibit increased Mll1 activity and genome-wide increased H3K4 tri-methylation at promoters. Null mutations of Mll1 in tumor mice and in xenotransplanted human head and neck tumors resulted in loss of self-renewal of tumor-propagating cells and in block of tumor formation but did not alter normal tissue homeostasis. CRISPR/Cas9 mutagenesis and pharmacological interference of Mll1 at sequences that inhibit essential protein-protein interactions or the SET enzyme active site also blocked the self-renewal of mouse and human tumor-propagating cells. Our work provides strong genetic evidence for a crucial role of Mll1 in solid tumors. Moreover, inhibitors targeting specific Mll1 interactions might offer additional directions for therapies to treat these aggressive tumors.

Tags
Antibody
iDeal ChIP-seq Kit for Histones
iDeal Library Preparation Kit

Share this article

Published
January, 2019

Source

Products used in this publication

  • cut and tag antibody icon
    C15410194
    H3K4me1 polyclonal antibody
  • cut and tag antibody icon
    C15410035
    H3K4me2 polyclonal antibody
  • cut and tag antibody icon
    C15410003-50
    H3K4me3 polyclonal antibody
  • ChIP kit icon
    C01010051
    iDeal ChIP-seq kit for Histones

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