Phokaew Chureerat, Kowudtitham Supakit, Subbalekha Keskanya, Shuangshoti Shanop, Mutirangura Apiwat
Inter-Department Program of BioMedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.
Nucleic Acids Res. 2008 Oct;36(17):5704-12. doi: 10.1093/nar/gkn571. Epub 2008 Sep 6.
This study evaluated methylation patterns of long interspersed nuclear element-1 (LINE-1) sequences from 17 loci in several cell types, including squamous cell cancer cell lines, normal oral epithelium (NOE), white blood cells and head and neck squamous cell cancers (HNSCC). Although sequences of each LINE-1 are homologous, LINE-1 methylation levels at each locus are different. Moreover, some loci demonstrate the different methylation levels between normal tissue types. Interestingly, in some chromosomal regions, wider ranges of LINE-1 methylation levels were observed. In cancerous cells, the methylation levels of most LINE-1 loci demonstrated a positive correlation with each other and with the genome-wide levels. Therefore, the loss of genome-wide methylation in cancerous cells occurs as a generalized process. However, different LINE-1 loci showed different incidences of HNSCC hypomethylation, which is a lower methylation level than NOE. Additionally, we report a closer direct association between two LINE-1s in different EPHA3 introns. Finally, hypermethylation of some LINE-1s can be found sporadically in cancer. In conclusion, even though the global hypomethylation process that occurs in cancerous cells can generally deplete LINE-1 methylation levels, LINE-1 methylation can be influenced differentially depending on where the particular sequences are located in the genome.
本研究评估了几种细胞类型(包括鳞状细胞癌细胞系、正常口腔上皮(NOE)、白细胞和头颈部鳞状细胞癌(HNSCC))中17个位点的长散在核元件1(LINE-1)序列的甲基化模式。尽管每个LINE-1的序列是同源的,但每个位点的LINE-1甲基化水平不同。此外,一些位点在正常组织类型之间表现出不同的甲基化水平。有趣的是,在一些染色体区域,观察到LINE-1甲基化水平的范围更广。在癌细胞中,大多数LINE-1位点的甲基化水平彼此之间以及与全基因组水平呈正相关。因此,癌细胞中全基因组甲基化的丧失是一个普遍过程。然而,不同的LINE-1位点显示出HNSCC低甲基化(即甲基化水平低于NOE)的不同发生率。此外,我们报告了不同EPHA3内含子中的两个LINE-1之间存在更紧密的直接关联。最后,某些LINE-1的高甲基化可在癌症中偶尔发现。总之,尽管癌细胞中发生的整体低甲基化过程通常会降低LINE-1甲基化水平,但LINE-1甲基化会因特定序列在基因组中的位置不同而受到不同影响。