PRESS RELEASE

• Researchers from the Differentiation and Cancer group of the Center for Genomic Regulation (CRG) have published an innovative study on the role of Cbx proteins in the genetic regulation of embryonic stem cells.
• The study revealed that changes in the expression of specific Polycomb group proteins modulate the function of the Polycomb complex during both embryonic stem cell differentiation and tumorigenesis.
• The article will be published in, and featured on the cover of, the 6 January issue of the journal Cell Stem Cell.

The Polycomb repressive complex 1 (PRC1) regulates the proliferation, and the subsequent differentiation into somatic cells, of embryonic stem (ES) cells, but the exact role of the different Polycomb proteins in this complex has been a long-standing puzzle. Researchers at the CRG have now elucidated the role that several specific Polycomb proteins (namely, Cbx2, -4, -6, -7, and -8) play during cell development through their incorporation into, and regulation by, the PRC1 complex. This discovery represents a breakthrough in understanding both how stem cells proliferate and which specific functions the Cbx proteins and the Polycomb PRC1 complex play during tumor development. Identifying new proteins that are essential for maintaining ES cell pluripotency is a key step in elucidating tumor formation processes and in advancing regenerative medicine.
Since its incorporation into the CRG, the group of Epigenetic Events in Cancer, lead by Dr. Luciano Di Croce, has focused on the biological functions of the Polycomb complex and its role during tumor progression. They have previously made important contributions to the field and have published articles in high impact journals such as Cancer Cell (in 2007) and Nature (in 2010). Now, they have tackled the question of how ES cell regulation by the Polycomb group proteins and complexes is fine-tuned: while it has been long known that this regulation occurs, nothing was known about whether the individual Polycomb proteins have specific functions. They discovered that, indeed, different Cbx proteins have distinct functions that can modulate the activity of the PRC1 complex, as they report in their article to be published in Cell Stem Cell on 6 January 2012.
ES cells are key for embryonic development. ES cells can divide (proliferate) extensively before they differentiate into the somatic cells that form the adult tissue. “We found that the protein Cbx7 is present during the proliferation phase, when the cells still maintain their pluripotency, but that Cbx7 is replaced with Cbx2 and Cbx4 during the differentiation phase. Exchanging one Cbx protein for another has important consequences for the pluripotent capacity of ES cells, tumor formation, and correct cellular differentiation,” says Lluis Morey, first author of the paper.
“We discovered that implanting ES cells depleted for the different specific Cbx proteins led to the mice developing tumors with different characteristics. This showed that each Cbx protein has a unique function. Even though there is no medical application at the present time, these results will surely generate research towards developing drugs that could block these type of proteins”, said Dr. Di Croce, ICREA Investigator and corresponding author of the study.
The study was done in collaboration with the CRG group of Epithelial Homeostasis and Cancer, headed by Dr. Salvador Aznar-Benitah, ICREA Investigator, and with Dr. Anton Wutz, from the Wellcome Trust Centre for Stem Cell Research, Cambridge. It was supported by grants from the Spanish ‘‘Ministerio de Educación y Ciencia’’ (CONSOLIDER program), the AGAUR, and a postdoctoral CRG-Novartis fellowship.

Reference: Morey, L. et al. (2012) Nonoverlapping Functions of the Polycomb Group Cbx Family of Proteins in Embryonic Stem Cells. Cell Stem Cell. doi:10.1016/j.stem.2011.12.006
Other publications on the subject from the Di Croce group:

• Villa, R. et al. (2007) Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia. Cancer Cell, 11:513-525. doi:10.1016/j.ccr.2007.04.009
• Richly, H. et al.  (2010) Transcriptional Activation of Polycomb-Repressed Genes by ZRF1. Nature 468:1124-1128. doi:10.1038/nature09574

The CRG press release of this paper can be found here.Terms:
Pluripotency: Pluripotency refers to the capacity of stem cells to differentiate into any one of the three different types of cells that make up the primary germ layers: the endoderm, mesoderm, or ectoderm. Pluripotent cells are distinct from totipotent cells as they cannot form extraembryonic tissue, such as the placenta. Thus, pluripotent cells can produce all of the organs within an organism but cannot be used to reproduce the organism itself, as their nuclei are not identical to those of zygotes. Currently, scientists can convert an adult cell into a pluripotent cell by manipulating its gene expression. Such "artificial" cells are termed induced pluripotent stem cells (iPS cells).
Embryonic stem cells (ES cells): ES cells are pluripotent cells that are derived from an early stage of embryonic development, the blastocyst. They have the capacity to differentiate into each of the distinct cells that form tissues.
Please visit www.eurostemcell.org for further information

For further information: Juan Sarasua, Press Office, Public Relations and Communication Dept., Center for Genomic Regulation (CRG). Tel. +34 93 316 02 37; e-mail: juan.sarasua@crg.eu
Image available to download at: ftp://jsarasua:jsa32rasua@perelman.crg.es