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Short‐Form CDYLb but not long‐form CDYLa functions cooperatively with histone methyltransferase G9a in hepatocellular carcinomas
Author(s) -
Wu Hui,
Zhang Haihong,
Wang Peng,
Mao Zhuo,
Feng Li,
Wang Yuqian,
Liu Chenlu,
Xia Qiu,
Li Bo,
Zhao Heya,
Chen Yan,
Wu Jiaxin,
Kong Wei,
Yu Xianghui
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22060
Subject(s) - hccs , histone h3 , methyltransferase , methylation , histone methyltransferase , biology , histone , lysine , epigenetics , effector , histone methylation , hepatocellular carcinoma , microbiology and biotechnology , biochemistry , gene expression , chemistry , gene , dna methylation , cancer research , amino acid
In hepatocellular carcinomas (HCCs), the levels of histone H3 dimethylation at lysine 9 (H3K9me2) and its corresponding histone methyltransferase G9a are significantly elevated. Recently, G9a was reported to form a complex with the H3K9 methylation effector protein CDYL, but little is known about the expression of CDYL in HCC patients. The human CDYL gene produces two transcripts, a long form ( CDYLa ) and a short form ( CDYLb) , but it is unclear whether the protein products have different functions. The aim of this study was to investigate the distinctions between CDYLa and CDYLb and their expression levels in HCC tissues. We first examined binding abilities of the different CDYL forms with methylated H3 peptides by a pull‐down assay. Human CDYLb (h‐CDYLb) specifically recognized H3Kc9me2 and H3Kc9me3 modifications, whereas human CDYLa (h‐CDYLa) did not interact with any methylated H3 peptides. Similarly, mouse CDYLb (m‐CDYLb) specifically bound with di‐ and tri‐methylated H3Kc9 peptides, while mouse CDYLa (m‐CDYLa) lacked that ability. Affinity purification also was used to identify the distinct composition of the h‐CDYLa or h‐CDYLb protein complex. h‐CDYLb was found in a multiprotein complex with G9a and GLP, while the h‐CDYLa complex did not contain these two enzymes. Consistent with the protein complex composition, h‐CDYLb and G9a were both upregulated in HCC tissues, compared with adjacent non‐cancerous liver tissues. Furthermore, the positive correlation between expression levels of h‐CDYLb and G9a was statistically significant. In contrast, h‐CDYLa showed no enrichment in HCC tissues. These findings suggest that h‐CDYLb and G9a are cooperatively involved in HCC. © 2013 Wiley Periodicals, Inc.