The Feb. 22, 2007 issue of Cell is a special review issue on epigenetics, surveying the landscape of what is known and what is not about the DNA modifications that are collectively known as epigenetics.
Part of the essays already may be out of date. In the Feb. 23, 2007, issue of Science, researchers from Harvard Medical School take on two widely held beliefs about one epigenetic mechanism, DNA methylation - neither of which appears to stand up to their data.
The 11 Cell papers that are part of the review issue aim to present "our current knowledge of the molecular basis of epigenetic mechanisms, including the emerging role of noncoding RNAs and their role in development and disease, and discusses the still largely unknown terrain of chromatin organization."
Epigenetics is a set of modifications to DNA that are able to pass on genetic information that is not encoded in the sequence itself. They include methylation of the DNA, as well as multiple types of modification to its chromatin packaging. Noncoding RNA is another way in which information that is not in the DNA sequence can be passed on to offspring.
While the detail of what is known about DNA replication can be mind-numbing, epigenetics remains a largely unexplored territory. It is clear that epigenetics play a role in normal as well as disease states, but the details largely remain to be worked out. (see BioWorld Today, Dec. 22, 2005.)
Topics in the Cell review issue include the timescales of epigenetic inheritance, the epigenomics of cancer, epigenetic regulators of stem cells and noncoding RNAs.
One good place to start understanding epigenetic modifications is the X chromosome. Because female mammals have two X chromosomes and men only one, one of the X chromosomes in women is switched off, via epigenetic modifications.
In the Science paper, Asaf Hellman and Andrew Chess report on the results of a chromosome-wide study of methylation patterns on the active and inactive X chromosomes.
Based on their findings, "we need to rethink the relationship between methylation, gene activity and chromatin state," first author Hellman told BioWorld Today.
The first idea that did not stand up to scrutiny was that it is the inactive X chromosome that is more methylated; specifically, that methylation of the promoters on the inactive X chromosome will shut them down and prevent gene expression.
Instead, Hellman said, "the active copy is the one that is more methylated." More than twice as methylated, as a matter of fact. The ratio of methylated sites on the active versus inactive chromosomes was 2.4
In the course of their experiments, Hellman and Chess also made another discovery challenging conventional wisdom. The general belief among cell biologists is that "once you pack up one chromosome for inactivation, you just spread the inactive state evenly along the chromosome," Hellman said. But "we found something very different - that methylation basically targets the gene body."
Hellman said he believes their findings about methylation and gene activity probably hold true for other chromosomes as well. "X is just a good place to find it, because of the active and the inactive one."