tailieunhanh - báo cáo khoa học: " Tackling the methylome: recent methodological advances in genome-wide methylation profiling"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Tackling the methylome: recent methodological advances in genome-wide methylation profiling | Genome Medicine Review Tackling the methylome recent methodological advances in genome-wide methylation profiling Marcos RH Estécio and Jean-Pierre J Issa Address Department of Leukemia UT MD Anderson Cancer Center Houston TX 77030 USA. Correspondence Jean-Pierre J Issa. Email jpissa@ Abstract DNA methylation of promoter CpG islands is strongly associated with gene silencing and is known as a frequent cause of loss of expression of tumor suppressor genes as well as other genes involved in tumor formation. DNA methylation of driver genes is very likely outnumbered by the number of methylated passenger genes though these can be useful as tumor markers. Much of what is known about the importance of DNA methylation in cancer was gained through small- and moderate-scale analysis of gene promoters and tumor samples. A much better understanding of the role of DNA methylation in cancer either as a marker of disease or as an active driver of tumorigenesis will likely be gained from genome-wide studies of this modification in normal and malignant cells. This goal has become more attainable with the recent introduction of large-scale genome analysis methodologies and these have been modified to allow for investigation of DNA methylation. Several research groups have been formed to coordinate efforts and apply these methodologies to decipher the methylome of healthy and diseased tissues. In this article we review technological advances in genome-wide methylation profiling. Introduction In mammals DNA methylation is predominantly if not exclusively found in CpG dinucleotides due to site specificity of the known DNA methyltransferases 1 . Although it was reported in the early 1960s that cytosines can be methylated it was not until two decades later that DNA methylation was fully recognized as an important player in gene regulation 2-4 . By acting coordinately with histone tail modifications and recruitment of an array of proteins involved in chromatin condensation