Christophe Herman, Ph.D.
Associate Professor of Molecular and Human Genetics
Ph.D., Universite libre de Bruxelles, 1996
Postdoc, Massachusetts Institute of Technology, 1997
Postdoc, University of California, San Francisco, 2004
Molecular Noise and Epigenetic Inheritance
Phenotypic inheritance relies on the correct transfer of the genetic (DNA) and epigenetic (heritable expression state) information. It is well established that DNA alteration can heritably change the phenotype of a cell, but what is less clear is what triggers heritable epigenetic change. Seminal work in bacteria has highlighted the importance of genetic networks in epigenetic inheritance. To generate stable phenotypic diversity in a population, cells with identical genomes can be differently programmed by transcription factors connected in a positive feedback loop, allowing the stable expression of two alternative phenotypes. Regulatory proteins associated with these molecular switches are often present in low numbers and therefore, subject to fluctuation or "molecular noise". Therefore, the strategy used by a genetic network to control levels of its key regulators is fundamental to the understanding of the potential sources of dysregulation. Molecular noise in gene expression is universal and arises as a result of the stochastic nature of transcription and translation and can directly perturb the behavior of genetic-regulatory-networks generating phenotypic diversity.
My lab is investigating the role of transient errors in information transfer (transcription, translation, or post-translational modification errors) in the dysregulation of bistable genetic networks leading to heritable change in phenotype. To study the contribution of information transfer errors on the generation of heritable phenotypic diversity, we are using classical bistable switches in the bacterium Escherichia coli; the bacteriophage lambda genetic switch; and the Lac operon.
With the exception of Prion inheritance, the idea that transient errors in information transfer from RNA to protein can have heritable consequences without any alteration of the DNA sequence has not been considered before, but our work challenge this idea by showing that transient alteration of autocatalytic systems can have profound heritable consequences. Thus, our work suggests that transient errors in information transfer may be an important mechanism of epigenetic change and should be considered as the causative agent for many human diseases ranging from the progression of AIDS to devastating neurodegenerative diseases.
- Gordon AJ, Satory D, Halliday JA, Herman C (2013). Heritable change caused by transient transcription errors. PLoS Genet. 9(6): e1003595. PubMed PMID: 23825966
- Satory D, Gordon AJ, Halliday JA, Herman C (2011). Epigenetic switches: can infidelity govern fate in microbes? Curr. Opin. Microbiol. 14(2): 212-7. PubMed PMID: 21496764
- Gibson JL, Lombardo MJ, Thornton PC, Hu KH, Galhardo RS, Beadle B, Habib A, Magner DB, Frost LS, Herman C, Hastings PJ, Rosenberg SM (2010). The sigma(E) stress response is required for stress-induced mutation and amplification in Escherichia coli. Mol. Microbiol. 77(2): 415-30. PubMed PMID: 20497332
- Tehranchi AK, Blankschien MD, Zhang Y, Halliday JA, Srivatsan A, Peng J, Herman C, Wang JD (2010). The transcription factor DksA prevents conflicts between DNA replication and transcription machinery. Cell 141(4): 595-605. PubMed PMID: 20478253
- Koodathingal P, Jaffe NE, Kraut DA, Prakash S, Fishbain S, Herman C, Matouschek A (2009). ATP-dependent proteases differ substantially in their ability to unfold globular proteins. J. Biol. Chem. 284(28): 18674-84. PubMed PMID: 19383601
- Blankschien MD, Lee JH, Grace ED, Lennon CW, Halliday JA, Ross W, Gourse RL, Herman C (2009). Super DksAs: substitutions in DksA enhancing its effects on transcription initiation. EMBO J. 28(12): 1720-31. PubMed PMID: 19424178
- Gordon AJ, Halliday JA, Blankschien MD, Burns PA, Yatagai F, Herman C (2009). Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network. PLoS Biol. 7(2): e44. PubMed PMID: 19243224
- Blankschien MD, Potrykus K, Grace E, Choudhary A, Vinella D, Cashel M, Herman C (2009). TraR, a homolog of a RNAP secondary channel interactor, modulates transcription. PLoS Genet. 5(1): e1000345. PubMed PMID: 19148274
- Nonaka G, Blankschien M, Herman C, Gross CA, Rhodius VA (2006). Regulon and promoter analysis of the E. coli heat-shock factor, sigma32, reveals a multifaceted cellular response to heat stress. Genes Dev. 20(13): 1776-89. PubMed PMID: 16818608
- Herman C, Thévenet D, Bouloc P, Walker GC, D'Ari R (1998). Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH). Genes Dev. 12(9): 1348-55. PubMed PMID: 9573051
Awards and Honors
2009: Michael E. DeBakey, M.D., Excellence in Research Award
Christophe Herman, Ph.D
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.