Epigenetic Alterations are Fundamental in Normal Development and Cancer
In eukaryotic cells, genomic DNA is packaged with proteins to form higher-order chromatin structures. Epigenetics refers to heritable phenotypic changes that are not mediated by changes in DNA sequence but instead are mediated by alterations in chromatin structure. This involves modifications to DNA (e.g., cytosine methylation and hydroxymethylation) and to histones (e.g., methylation, acetylation, phosphorylation and ubiquitination) by a variety of enzymes.
Importantly, many of these chromatin-modifying enzymes are mutated in cancers, and epigenetic alterations may be just as important as DNA mutations in driving cancer. In addition to controlling gene transcription, these chromatin-modifying enzymes regulate other processes requiring the genetic material including DNA replication and repair. Epigenetic mechanisms thus unite a number of different research areas within the department.
Specific departmental research efforts in epigenetics include:
- The biological roles of histone tail lysine and arginine methylation
- Identification and characterization of “readers” of epigenetic marks
- The role of histone acetylation in the DNA damage response
- Crosstalk between histone modifications and DNA methylation
- Crosstalk between histone modifications and modifications of non-histone substrates
- Epigenetics of developmental reprogramming.
Importantly, epimutations, unlike genetic mutations, can be reversed by chemotherapeutic intervention, which makes epigenetic therapy conceptually appealing. Efforts are underway in the department to screen and identify small-molecule regulators of epigenetic modifiers and evaluate their potential as anti-cancer drugs, providing clear translational relevance to this research.
The Center for Cancer Epigenetics
Many faculty members in the department are active participants in the Center for Cancer Epigenetics (CCE), one of several components of MD Anderson’s Institute for Basic Science.