For normal development, cells must pass on their gene expression patterns to their daughter cells. The DNA in different cells is the same. Therefore the mark that establishes which genes are on and which are off in a given cell must be epigenetic, and is probably a direct or indirect consequence of changes in chromatin structure. This epignetic mark must also be stable to mitosis. Despite 25 years of searching, we still don’t have a clear idea what the epienetic mark is, how the it is established, and how the epigenetic mark is interpreted to regulate transcription. One clue comes from the observations that mutations in Polycomb group (PcG) genes fail to maintain gene expression patterns. PcG genes encode chromatin proteins, the modify histones, or change nucleosome positioning, or have unknown functions. My laboratory studies how PcG proteins are required for maintenance of gene expression in Drosophila. Our overall goal is to understand how Polycomb group proteins function at the molecular level in maintenance. Currently, we are attempting to develop new methods of establishing the details of how maintenance is established in homeotic genes during development. We are also examining the role of PcG proteins in the cell cycle. Trithorax group (trxG) proteins maintain gene activation. We study Asx, a protein that is required for both PcG and trxG activity.
Very recently we have discovered an unexpected connection between long non-coding RNAs and repression of homeotic genes. We are determining the molecular mechanism of RNA-mediated repression, and determining how this repression is integrated with PcG-dependent silencing.
Students coming to my lab are exposed to genetic, developmental, molecular, and biochemical approaches to studying questions in a developmental system. I encourage students to develop their own projects, to work independently, and to collaborate as necessary to maximize productivity.
Director of the Genetics Graduate Program
EMBO Post-doctoral Fellow, Univ of Paris (1981)
Jane Coffin Childs Fellow, Univ. of Washington (1981)
Associate Member, Medical Genetics Dept., UBC
Associate Member, Biotechnology Lab., UBC
President of the Genetics Society of Canada 2002-2003
Killam Teaching Award (2002)
- Mohd-Sarip, A., Lagarou, A., Doyen, C.M., van der Knaap, J.A., Aslan, U., Bezstarosti, K., Yassin, Y., Brock, H.W., Demmers, J.A., C.P. Verrijzer 2012. Transcription-independent function of Polycomb group protein PSC in cell cycle control. Science 336: 744-7
- Petruk, S., Johnston, D.M., Sedkov, Y., Hodgson, J.W., Black, K.L., Beck, S., Cananni, E., Brock, H.W., A. Mazo 2012. TrxG and Pcg proteins but not methylated histones remain associated with their response elements during DNA replication. Cell 150:922-33
- Hodgson, J.W., H.W. Brock 2011. Are Polycomb Group bodies gene silencing factories. Cell 144: 170-171
- Beck, S.A., O’Dor, E., Catching, A., Brock, H.W 2010. Cell cycle defects in polyhomeotic mutants are caused by abrogation of the DNA damage checkpoint. Dev. Biol. 339:320-328
- Fisher CL, Pineault N, Brookes C, Helgason CD, Ohta H, Bodner C, Hess JL, Humphries RK, Brock HW 2010. Loss-of-function Additional sex combs like 1 mutations disrupt hematopoiesis but do not cause severe myelodysplasia or leukemia. Blood 115:38-46