Prof. Winship Herr, Full Professor

Center for Integrative Genomics UNIL Genopode Building CH-1015 Lausanne Tel:  +41 21 692 39 22 Fax: +41 21 692 39 25 E-mail: winship.herr@unil.ch 4 post-doctoral fellows 3 doctoral students

Research activities :

• Regulation of cell proliferation and differentiation

Research key words :

• Cell-cycle; differentiation; transcription; herpes simplex virus; cancer

Link to our website

Two complete sets of instructions contained within the genomes we inherit from each of our parents are responsible for directing a single cell - the zygote - to become an adult human being. This process results from controlled patterns of gene expression that are maintained as well as changed during many rounds of cell division, differentiation, and death. Control of gene transcription is fundamental to these processes, with genetic and epigenetic defects in transcriptional regulation often leading to human disease including cancer.

To investigate these processes, we study an emerging key regulator of the human cell-proliferation cycle that was originally discovered in studies of herpes simplex virus (HSV) transcription - the HSV host-cell factor HCF-1. Recent studies reveal that HCF-1 plays important roles in chromosome function at distinct stages of the cell cycle.

HCF-1 is unusual. It is an abundant, conserved, and chromatin-bound protein that is proteolytically cleaved into stably associated amino- (HCF-1n) and carboxy- (HCF-1c) terminal subunits. The HCF-1n and HCF-1c subunits play roles in two separate cell-cycle phases: the G1 and M phases, respectively. Consistent with pivotal roles in these processes, the HCF-1n subunit associates with regulators of G1-phase transcription, whereas the HCF-1c subunit controls chromosome dynamics and histone modification during mitosis. We hypothesize that the two different subunits, via regulated self-association, influence each other's activity and help coordinate the M/G1 phase of the cell cycle. Our current interests focus on understanding how HCF-1 regulates cell proliferation - especially as it pertains to cancer - and cell differentiation.

Representative publications :

• Tyagi S, Chabes AL, Wysocka J, Herr W. (2007) E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol Cell 27:107-119.

• Capotosti F, Hsieh JJ, Herr W. (2007) Species selectivity of mixed-lineage leukemia/trithorax and HCF proteolytic maturation pathways. Mol Cell Biol 27:7063-7072.

• Tyagi, S. and Herr, W. (2009) E2F1 mediates DNA damage and apoptosis via HCF-1 and the MLL family of histone methyltransferases. EMBO J. (in press).