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 weshow 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9671-9676 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | 21 |
| DOIs | |
| State | Published - May 25 2010 |
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Keywords
- Breast cancer
- Cell cycle
- Epigenetics
- JmjC
- Transcription
ASJC Scopus subject areas
- General
Cite this
KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation. / Hsia, Datsun A.; Tepper, Clifford G; Pochampalli, Mamata R.; Hsia, Elaine Y C; Izumiya, Chie; Huerta, Steve B.; Wright, Michael E.; Chen, Hongwu; Kung, Hsing-Jien; Izumiya, Yoshihiro.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 21, 25.05.2010, p. 9671-9676.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation
AU - Hsia, Datsun A.
AU - Tepper, Clifford G
AU - Pochampalli, Mamata R.
AU - Hsia, Elaine Y C
AU - Izumiya, Chie
AU - Huerta, Steve B.
AU - Wright, Michael E.
AU - Chen, Hongwu
AU - Kung, Hsing-Jien
AU - Izumiya, Yoshihiro
PY - 2010/5/25
Y1 - 2010/5/25
N2 - 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 weshow 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.
AB - 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 weshow 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.
KW - Breast cancer
KW - Cell cycle
KW - Epigenetics
KW - JmjC
KW - Transcription
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U2 - 10.1073/pnas.1000401107
DO - 10.1073/pnas.1000401107
M3 - Article
C2 - 20457893
AN - SCOPUS:77953084666
VL - 107
SP - 9671
EP - 9676
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 21
ER -