ePrints

ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation

Lookup NU author(s): Dr Olivier Binda

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

Aberrations in chromatin dynamics play a fundamental role in tumorigenesis, yet relatively little is known of the molecular mechanisms linking histone lysine methylation to neoplastic disease. ING4 (Inhibitor of Growth 4) is a native subunit of an HBO1 histone acetyltransferase (HAT) complex and a tumor suppressor protein. Here we show a critical role for specific recognition of histone H3 trimethylated at lysine 4 (H3K4me3) by the ING4 PHD finger in mediating ING4 gene expression and tumor suppressor functions. The interaction between ING4 and H3K4me3 augments HBO1 acetylation activity on H3 tails and drives H3 acetylation at ING4 target promoters. Further, ING4 facilitates apoptosis in response to genotoxic stress and inhibits anchorage-independent cell growth, and these functions depend on ING4 interactions with H3K4me3. Together, our results demonstrate a mechanism for brokering crosstalk between H3K4 methylation and H3 acetylation and reveal a molecular link between chromatin modulation and tumor suppressor mechanisms.

Publication metadata

Author(s): Hung T, Binda O, Champagne KS, Kuo AJ, Johnson K, Chang HY, Simon MD, Kutateladze TG, Gozani O

Publication type: Article

Publication status: Published

Journal: Molecular Cell

Year: 2009

Volume: 33

Issue: 2

Pages: 248-256

ISSN (print): 1097-2765

ISSN (electronic): 1097-4164

Publisher: Elsevier Inc

URL: http://dx.doi.org/10.1016/j.molcel.2008.12.016

DOI: 10.1016/j.molcel.2008.12.016

PubMed id: 19187765

Altmetrics

Share