Sachan Manisha, Raman Rajiva
Department of Biotechnology, Institute of Biosciences and Biotechnology, C.S.J.M. University, Kanpur-208024, India.
Gene. 2008 Jun 15;416(1-2):22-9. doi: 10.1016/j.gene.2008.02.024. Epub 2008 Mar 18.
We have studied the dynamics of de novo DNA methylation of 16 contiguous CpGs in the non-CpG island-coding region of the proto-oncogene c-fos during mouse development by Na-bisulfite sequencing. Methylation commences from 16.5 dpc and occurs in stepwise-manner. In liver 7 sites are methylated between 16.5 dpc and day 5 after birth, but all the sites are completely methylated on 20 dpp and remain so in the adult liver. The present study provides evidence that (1) pattern of methylation of c-fos is distinct from those DNA sequences which methylate pre- and post-implantation, both in terms of the timing and spreading, and (2) spacing of CpGs is an important factor in determining the course of methylation. We suggest that there could be other isoforms of Dnmtases for the c-fos like embryonic genes, not only because they methylate later in development but also because of the difference in kinetics of the reaction, and that the nucleation of certain methylated sites facilitate methylation of neighbouring sites and their maintenance in subsequent cell generations.
我们通过亚硫酸氢钠测序研究了原癌基因c-fos的非CpG岛编码区中16个相邻CpG位点的从头DNA甲基化动力学，该过程发生在小鼠发育期间。甲基化始于胚胎发育第16.5天，并以逐步的方式进行。在肝脏中，7个位点在胚胎发育第16.5天至出生后第5天之间发生甲基化，但所有位点在出生后第20天完全甲基化，并在成年肝脏中保持这种状态。本研究提供了以下证据：（1）c-fos的甲基化模式在时间和扩散方面均不同于着床前和着床后甲基化的DNA序列；（2）CpG位点的间距是决定甲基化进程的重要因素。我们认为，可能存在其他类似于胚胎基因c-fos的DNA甲基转移酶同工型，这不仅是因为它们在发育后期发生甲基化，还因为反应动力学存在差异，并且某些甲基化位点的成核促进了相邻位点的甲基化及其在后续细胞世代中的维持。
