Molecular Medicine & Pathology seminar: Cohesin: The Glue That Links Cell Proliferation With Developmental Programmes Event as iCalendar

04 April 2013

3:30 - 4:30pm

Venue: Seminar Room 501-505, Building 501, 85 Park Road, Grafton

A recently fertilised embryo contains rapidly dividing cells that have the potential to develop into any part of the body.  One of life's biggest mysteries is how cells in the early embryo decide what to be.  Cohesin proteins are essential for both chromosome duplication and for controlling expression of specific developmental genes.  Cohesin also regulates genes that promote stem cell identity.  Therefore, this protein complex could form a vital link between cell division and differentiation.

In zebrafish and in MCF-7 breast cancer cells, we have shown that cohesin positively regulates the expression of the oncogene Myc.  In MCF-7 cells, cohesin depletion prevents oestradiol induction of MYC transcription.  Along with Sox2, Oct4 and Nanog, Myc plays a crucial role in embryonic stem cell proliferation and pluripotency.  To better understand cohesin’s role in pluripotency, we sought to identify genes bound (and therefore potentially regulated) by cohesin in pluripotent cells of the zebrafish embryo.  Chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) on blastula staged zebrafish embryos revealed that cohesin binds to the regulatory regions of genes that encode pluripotency transcription factors (oct4, sox2), histone variants (h2afx, h2afy2, h3f3a) and histone modifiers (myst3, bmi1, pcgf1, epc2) indicating cohesin has potential to directly regulate their expression.  Genes in these categories are also strongly upregulated in rapid-cycling mouse ES cells, implying that factors controlling epigenetic modification of DNA are crucial for transcriptional programming of the embryo.

Research from our lab using the zebrafish animal model has provided several examples where a transcriptional role of cohesin links cell proliferation to differentiation, leading us to focus on the mechanism of gene regulation by cohesin.  For example, cohesin controls tissue-specific transcription of the runx1 gene (which is important for hematopoietic stem cell development) via interaction with the runx1 promoters and specific cis-regulatory elements.  These findings will be presented in context of the notion that the multiple functions of cohesin may represent a major control point for specification of cell fate.

Followed by drinks and pizza