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Studies on Functional Role of DNA Methylation within the FXYD5-COX7A1 Region of Human Chromosome 19

Y. V. Skvortsova, T. L. Azhikina*, E. A. Stukacheva, and E. D. Sverdlov

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia; fax: (495) 330-6536; E-mail: tanya@humgen.siobc.ras.ru

* To whom correspondence should be addressed.

Received January 30, 2009; Revision received February 18, 2009
We used the Rapid Identification of Genomic Splits technique to get a detailed methylation landscape of a 1‑megabase-long human genome region (FXYD5-COX7A1, chromosome 19) in normal and tumor lung tissues and in the A549 lung cancer cell line. All three samples were characterized by an essentially uneven density of unmethylated sites along the fragment. Strikingly enough, the distribution of hypomethylated regions did not correlate with gene locations within the fragment. We also demonstrated that the methylation pattern of this long genomic DNA fragment was rather stable and practically unchanged in human lung cancer tissue as compared with its normal counterpart. On the other hand, the methylation landscape obtained for the A549 cell line (human lung carcinoma) in the USF2-MAG locus showed clear differences from that of the tissues mentioned above. A comparative analysis of transcriptional activity of the genes in this region demonstrated the general absence of direct correlation between methylation and expression, although some data suggest a possible role of methylation in the regulation of MAG expression through cis‑regulatory elements. In total, our data provide new evidence for the necessity of revising currently prevailing views on the functional significance of methyl groups in genomic DNA.
KEY WORDS: methylation profile, regulation of gene expression, MAG, HAMP

DOI: 10.1134/S0006297909080082