Department of Molecular and Human Genetics
Dr. Herman received the award for his work in epigenetic inheritance and transcription regulation.
Dr. Herman's work has provided an important new paradigm for epigenetic inheritance. Previously, study of heritable phenotypic change had focused on errors in DNA, or "the hardware of the cell". Dr. Herman's work has shown that errors in genetic networks, the "software of the cell", also affects phenotypic inheritance, through errors in mRNA transcription. This demonstrated a new mechanism of epigenetic variation, whereby RNA errors can mimic DNA errors. Additionally, Dr. Herman's work showed that transcription errors contribute to gene expression stochastically or as molecular noise, a feature shown to be important for stem cell pluripotency. Because of the universal nature of transcription, this is a phenomenon inherent to all organisms. It is important to the understanding of human disease linked to epigenetic modification as for example in cancer or prion formation.
Dr. Herman and colleagues also described a novel mechanism of gene regulation associated with transcription factors. Small proteins can regulate transcription initiation through a secondary channel of RNA polymerase. This channel was previously thought to be mediated by a small nucleotide found only in a few bacterial species. These findings suggest that this type of regulation may be more universal than previously thought.
Dr. Herman's nomination was based on the following publications:
Gordon AJ, Halliday JA, Blankschien MD, Burns PA, Yatagai F, Herman C. Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network. PloS Biol 7: e1000044, 2009.
Blankschien MD, Potrykus K, Grace E, Choudhary A, Vinella D, Cashel M, Herman C. TraR, a homolog of a RNAP secondary channel interactor, modulates transcription. PloS Genet 5:e1000345, 2009. PMID: 19148274
Blankschien MD, Lee JH, Grace ED, Lennon CW, Halliday JA, Ross W, Gourse RL, Herman C. Super DksAs: substitutions in DksA enhancing its effects of transcription initiation. EMBO J. 28:1720-31, 2009. PMID: 19424178