engleski

Various EZH2 transcript variants are present in cancer cell lines

Trimethylation of lysine 27 in histone H3 (H3K27me3) is a crucial epigenetic mark that is needed for gene silencing, maintaining stem cell pluripotency and proper cellular differentiation. The establishment of this epi-mark depends on the activity of methyltransferase Enhancer of Zeste Homolog 2 (EZH2), which acts as a catalytical subunit of the Polycomb Repressive Complex 2 (PRC2). This enzyme plays an important part in various types of cancers. Depending on the cancer type/specific cellular epi-network, EZH2 can function as an oncogene (prostate cancer) or as a tumor suppressor (myeloid malignancies). According to the GenBank database, there are five experimentally confirmed EZH2 transcript variants (TV1 – TV5). The longest transcript (TV1 ; NM_004456.4 ; 2724 bases) is composed of 20 exons. By comparison with this transcript, TV2-TV5 lack an in-frame segment that is composed of 15 nucleotides in exon 8 (ex8D15). In addition to ex8D15, TV2 also lacks exon 4, while both TV4 and TV5 lack an in-frame segment composed of 27 nucleotides in exon 3 (ex3D27). In addition to this, TV5 lacks exon 14. Here we report two novel transcript variants. One variant (TVexon427), lacking both exon 4 and 27 nucleotides in exon 3, is present in embryonic fibroblasts and three different cancer cell lines under resting conditions and after exposure to various types of stress. The second newly discovered variant, TVins126, is present in Detroit 562 cells grown in medium without glucose for 24 hours. This transcript includes an in-frame insertion of a part of intron 14 (N=126 bases), resulting in premature STOP codon. The importance of different EZH2 transcripts in such cellular processes as proliferation, differentiation, as well as cancer cell colony forming and cancer cell migration, has been only recently addressed. The biological significance of EZH2 transcript variants discovered by our research group is the focus of our ongoing research.

EZH2 ; aberrant splicing ; sequencing

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