Falk lecture features NYU epigenetics researcher
By Robin Arnette
The Hans L. Falk Memorial Lecture honors the memory of a scientist who was one of the founding members of NIEHS and an unwavering advocate for the study of how the environment influences disease. Fittingly, this lecture series features investigators who have made significant contributions to research related to environmental health sciences.
This year’s lecture Feb. 14 featured Danny Reinberg, Ph.D. (http://www.med.nyu.edu/biochem/ReinbergLab/index.html) a researcher who studies how epigenetics regulates gene expression. Reinberg is a Howard Hughes Medical Institute investigator and professor of biochemistry at New York University School of Medicine. He presented a seminar titled, “Molecular Mechanisms of Epigenetic Inheritance.” NIEHS Deputy Director Rick Woychik, Ph.D., served as host.
According to Reinberg, the field of epigenetics is the study of the heritable alterations to the genome that don't involve a change in the DNA sequence. Although epigenetics is still in its infancy, Reinberg said that the term was actually coined centuries ago by the Greek philosopher Aristotle. It wasn't until the mid-1940s that British biologist Conrad Waddington, Ph.D., offered an explanation for what it meant.
“He thought that within the development of an individual, phenotypic or outwardly-appearing changes happen without any modification of the genes,” Reinberg said. “What we have to keep in mind is stem cells and differentiated cells have identical genomes. The only distinction is they have different profiles of gene expression.”
Reinberg’s lecture focused on his interest in how DNA wraps around histones, which are the structural proteins of chromosomes, and the distinct modifications that take place on histone tails. He explained that these histone modifications — acetylation, methylation, phosphorylation, ubiquitination, and others — can either allow or repress transcription. He also said that the proteins that make these changes may be targets for drug therapy.
“The enzymes that do this are grouped into writers, readers, and erasers, and are mutated in many cancers,” he said. “Several companies have developed therapeutic strategies that attempt to circumvent their action on DNA.”
Unraveling the complexities of epigenetics
Some of Reinberg’s recent research suggests that certain methyl groups added to the histone proteins of a particular organism’s chromatin, which is DNA plus histones, also appear in the new cell when the original cell divides. This action ensures that the same pattern of gene expression is reproduced. Reinberg’s group determined that JARID2 is involved in the process and does its work in concert with several other proteins. JARID2, a human gene that encodes a protein required for proper development of an embryo, has a DNA binding domain and a domain that allows it to bind to and invigorate the multi-enzyme complex that performs the methylation that is also required for proper embryogenesis.
Reinberg will continue his studies on how epigenetic changes occur but, strangely enough, he didn’t start out in science interested in this topic. He said he began working with transcription but, as he dug deeper, the experiments kept pointing him to the histone modifications that were important for transcription.
“We wound up with gene products that were methylating here and there,” Reinberg added. “That’s where the science took me.”
Woychik summed up Reinberg’s work by saying it was truly on the cutting edge of understanding the molecular biology of epigenetic regulation of the mammalian genome.
“Epigenetics has changed our thinking on how the environment can influence human health and biology,” he said. “Reinberg’s research has had an enormous impact on the field of epigenetics research.”