KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation

Datsun A Hsia; Clifford G Tepper; Mamata R Pochampalli; Elaine Y.C Hsia; Chie Izumiya; Steve B Huerta; Michael E Wright; Hong-Wu Chen; Hsing-Jien Kung; Yoshihiro Izumiya

doi:10.1073/pnas.1000401107

Back

KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation

Journal article

Open access

Peer reviewed

KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation

Datsun A Hsia, Clifford G Tepper, Mamata R Pochampalli, Elaine Y.C Hsia, Chie Izumiya, Steve B Huerta, Michael E Wright, Hong-Wu Chen, Hsing-Jien Kung and Yoshihiro Izumiya

Proceedings of the National Academy of Sciences of the United States, Vol.107(21), pp.9671-9676

05/25/2010

DOI: 10.1073/pnas.1000401107

PMCID: PMC2906833

PMID: 20457893

Files and links (1)

url

https://doi.org/10.1073/pnas.1000401107View

Published (Version of record) Open Access

Abstract

Localized chromatin modifications of histone tails play an important role in regulating gene transcription, and aberration of these processes leads to carcinogenesis. Methylated histone lysine residues, a key player in chromatin remodeling, are demethylated by the JmjC class of enzymes. Here we show that JMJD5 (now renamed KDM8), a JmjC family member, demethylates H3K36me2 and is required for cell cycle progression. Chromatin immunoprecipitation assays applied to human genome tiling arrays in conjunction with RNA microarray revealed that KDM8 occupies the coding region of cyclin A1 and directly regulates transcription. Mechanistic analyses showed that KDM8 functioned as a transcriptional activator by inhibiting HDAC recruitment via demethylation of H3K36me2, an epigenetic repressive mark. Tumor array experiments revealed KDM8 is overexpressed in several types of cancer. In addition, loss-of-function studies in MCF7 cells leads to cell cycle arrest. These studies identified KDM8 as an important cell cycle regulator.

Physiological aspects

Histones

Genetic aspects

Research

Carcinogenesis

Cyclins

Details

Title: Subtitle: KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation
Creators: Datsun A Hsia
Clifford G Tepper
Mamata R Pochampalli
Elaine Y.C Hsia
Chie Izumiya
Steve B Huerta
Michael E Wright - University of Iowa, Molecular Physiology and Biophysics
Hong-Wu Chen
Hsing-Jien Kung
Yoshihiro Izumiya
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences of the United States, Vol.107(21), pp.9671-9676
Publisher: National Academy of Sciences
DOI: 10.1073/pnas.1000401107
PMID: 20457893
PMCID: PMC2906833
ISSN: 0027-8424
eISSN: 1091-6490
Language: English
Date published: 05/25/2010
Description audience: Academic
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9983759098202771

Metrics

24 Record Views

151 Times Cited - Web of Science