Epigenetics

Epigenetics

The word epigenetic simply means "factors which are outside of the genes". It reflects the complex reality that our genes can be influenced by the environment, which means our lifestyle can impact the expression of our genes. Epigenetics is the field that studies the relationship between our environment and our genes.

In classical molecular genetics, we are often taught that genes and alleles are what matters. However, in reality this is just part of the story. Within the cell, DNA is intertwined with a system of proteins and other molecules, forming a highly complex structure called chromatin.

The appearance and behaviour of chromatin can be changed by the addition or removal of small proteins called histones. There are many different types of histones, each with a specific role. Changes in chromatin structure by the addition of removal of histones can profoundly affect the activity of genes and, importantly, can be passed from one generation of cells to the next. This is most apparent in calico cats where epigenetic changes determine fur colour. In humans, environment, health and diet can have enormous impact on the epigenetic state and can contribute to diverse diseases.

For instance, a large number of proteins involved in cancer function through the modification of chromatin structures, interfering with normal chromatin function. For this reason, the chromatin is emerging as a prime target for the therapeutic intervention of many illnesses.

Our Research

Our epigenetics research group, led by Dr. Michael Kobor, seeks to answer some of the most fundamental questions in chromatin biology. These queries include how distinct chromosomal neighborhoods are established, how they function and interact with enzymes involved in DNA metabolism, how chromatin-remodeling complexes are regulated, and how histone variants and canonical histones are different from one another.

Many different environmental factors affect the molecular machinery of the DNA packaging process. We are involved in collaborations to elucidate this relationship in fetal alcohol spectrum disorder (FASD), asthma, and chronic obstructive pulmonary disease (COPD). We are also working with psychologists and population health scientists to study the effects of socio-economic status on gene expression.

Publications

Kobor MS, Archambault J, Lester W, Holstege FC, Gileadi O, Jansma DB, Jennings EG, Kouyoumdjian F, Davidson AR, Young RA, Greenblatt J. An unusual eukaryotic protein phosphatase required for transcription by RNA polymerase II and CTD dephosphorylation in S. cerevisiae. Mol. Cell 4(1):55-62. (1999) PMID 10445027

Kobor MS, Venkatasubrahmanyam S, Meneghini MD, Gin JW, Jennings JL, Link AJ, Madhani HD, Rine J. A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin. PLoS Biol. 2(5):E131. (2004) PMID 15045029

Roberts TM, Kobor MS, Bastin-Shanower SA, Ii M, Horte SA, Gin JW, Emili A, Rine J, Brill SJ, Brown GW. Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4. Mol. Biol. Cell 17(1):539-48. (2006) PMID 16267268