The old idea of biology was that who you are is a matter of which genes you have. It is now clear that an equally important issue is which genes you use. Like all of biology, this issue has chemistry at its core.
The cells of the early embryo can develop into any tissue type. But as the embryo grows, these so-called pluripotent stem cells differentiate, acquiring specific roles (such as blood, muscle or nerve cells) that remain fixed in their progeny. The formation of the human body is a matter of chemically modifying the stem cells’ chromosomes in ways that alter the arrays of genes that are turned on and off.
One of the revolutionary discoveries in research on cloning and stem cells, however, is that this modification is reversible and can be influenced by the body’s experiences. Cells do not permanently disable genes during differentiation, retaining only those they need in a “ready to work” state. Rather the genes that get switched off retain a latent ability to work—to give rise to the proteins they encode— and can be reactivated, for instance, by exposure to certain chemicals taken in from the environment.
What is particularly exciting and challenging for chemists is that the control of gene activity seems to involve chemical events happening at size scales greater than those of atoms and molecules—at the so-called mesoscale—with large molecular groups and assemblies interacting. Chromatin, the mixture of DNA and proteins that makes up chromosomes, has a hierarchical structure. The double helix is wound around cylindrical particles made from proteins called histones, and this string of beads is then bundled up into higher-order structures that are poorly understood. Cells exercise great control over this packing—how and where a gene is packed into chromatin may determine whether it is active or not.
Cells have specialized enzymes for reshaping chromatin structure, and these enzymes have a central role in cell differentiation. Chromatin in embryonic stem cells seems to have a much looser, open structure: as some genes fall inactive, the chromatin becomes increasingly lumpy and organized. “The chromatin seems to fix and maintain or stabilize the cells’ state,” says pathologist Bradley Bernstein of Massachusetts General Hospital.
What is more, such chromatin sculpting is accompanied by chemical modification of both DNA and histones. Small molecules attached to them act as labels that tell the cellular machinery to silence genes or, conversely, free them for action. This labeling is called “epigenetic” because it does not alter the information carried by the genes themselves.
The question of the extent to which mature cells can be returned to pluripotency— whether they are as good as true stem cells, which is a vital issue for their use in regenerative medicine—seems to hinge largely on how far the epigenetic marking can be reset.
It is now clear that beyond the genetic code that spells out many of the cells’ key instructions, cells speak in an entirely separate chemical language of genetics— that of epigenetics. “People can have a genetic predisposition to many diseases, including cancer, but whether or not the disease manifests itself will often depend on environmental factors operating through these epigenetic pathways,” says geneticist Bryan Turner of the University of Birmingham in England.
Source of Information : Scientific American Magazine