Epigenetic Alterations are Fundamental to Normal Development and Carcinogenesis
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
Epigenetics-based Research Provides New Avenues for Cancer Treatment
Epimutations, unlike genetic mutations, can be reversed by chemotherapeutic intervention, which makes epigenetic therapy conceptually appealing. Researchers in the department are screening and identifying small-molecule regulators of epigenetic modifiers and evaluating 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 centers within the MD Anderson Institute for Basic Science. The ultimate goal of the center is to define the full spectrum of epigenetic changes that occur in cancers, to discover the molecular causes of these changes, and to translate that newly gained knowledge into the clinic in the form of novel, epigenetic-based therapies.