RRC ID 28430
Author Chevillard-Briet M, Quaranta M, Grézy A, Mattera L, Courilleau C, Philippe M, Mercier P, Corpet D, Lough J, Ueda T, Fukunaga R, Trouche D, Escaffit F.
Title Interplay between chromatin-modifying enzymes controls colon cancer progression through Wnt signaling.
Journal Hum Mol Genet
Abstract Cancer progression is associated with epigenetic alterations, such as changes in DNA methylation, histone modifications or variants incorporation. The p400 ATPase, which can incorporate the H2A.Z variant, and the Tip60 histone acetyltransferase are interacting chromatin-modifying proteins crucial for the control of cell proliferation. We demonstrate here that Tip60 acts as a tumor suppressor in colon, since mice heterozygous for Tip60 are more susceptible to chemically induced preneoplastic lesions and adenomas. Strikingly, heterozygosity for p400 reverses the Tip60-dependent formation of preneoplastic lesions, uncovering for the first time pro-oncogenic functions for p400. By genome-wide analysis and using a specific inhibitor in vivo, we demonstrated that these effects are dependent on Wnt signaling which is antagonistically impacted by p400 and Tip60: p400 directly favors the expression of a subset of Wnt-target genes and regulators, whereas Tip60 prevents β-catenin acetylation and activation. Taken together, our data underline the physiopathological importance of interplays between chromatin-modifying enzymes in the control of cancer-related signaling pathways.
Volume 23(8)
Pages 2120-31
Published 2014-4-15
DOI 10.1093/hmg/ddt604
PII ddt604
PMID 24287617
MeSH Acetylation Animals Blotting, Western Cells, Cultured Chromatin / metabolism Chromatin Immunoprecipitation Colonic Neoplasms / genetics Colonic Neoplasms / metabolism* Colonic Neoplasms / pathology* Disease Progression Female Gene Expression Profiling Histone Acetyltransferases / metabolism Histone Acetyltransferases / physiology* Histones / metabolism* Inositol 1,4,5-Trisphosphate Receptors / physiology* Lysine Acetyltransferase 5 Male Mice Mice, Inbred C57BL Mice, Knockout Precancerous Conditions / genetics Precancerous Conditions / metabolism Precancerous Conditions / pathology Protein Processing, Post-Translational RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Trans-Activators / physiology* Wnt Proteins / genetics Wnt Proteins / metabolism* beta Catenin / metabolism
IF 5.101
Times Cited 17
WOS Category GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Mice RBRC01774