Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cellsvan den Boom, V., Rozenveld-Geugien, M., Bonardi, F., Malanga, D., van Gosliga, D., Heyink, A. M., Viglietto, G., Morrone, G., Fusetti, F., Vellenga, E. & Schuringa, J. J., 28-Mar-2013, In : Blood. 121, 13, p. 2452-2461 10 p.
Research output: Contribution to journal › Article › Academic › peer-review
The Polycomb group (PcG) protein BMI1 is a key factor in regulating hematopoietic stem cell (HSC) and leukemic stem cell self-renewal and functions in the context of the Polycomb repressive complex 1 (PRC1). In humans, each of the 5 subunits of PRC1 has paralog family members of which many reside in PRC1 complexes, likely in a mutually exclusive manner, pointing toward a previously unanticipated complexity of Polycomb-mediated silencing. We used an RNA interference screening approach to test the functionality of these paralogs in human hematopoiesis. Our data demonstrate a lack of redundancy between various paralog family members, suggestive of functional diversification between PcG proteins. By using an in vivo biotinylation tagging approach followed by liquid chromatography-tandem mass spectrometry to identify PcG interaction partners, we confirmed the existence of multiple specific PRC1 complexes. We find that CBX2 is a nonredundant CBX paralog vital for HSC and progenitor function that directly regulates the expression of the cyclin-dependent kinase inhibitor p21, independently of BMI1 that dominantly controls expression of the INK4A/ARF locus. Taken together, our data show that different PRC1 paralog family members have nonredundant and locus-specific gene regulatory activities that are essential for human hematopoiesis.
|Number of pages||10|
|Publication status||Published - 28-Mar-2013|
- POLYCOMB GROUP PROTEINS, IMPAIRS SELF-RENEWAL, HUMAN CD34(+) CELLS, STEM-CELLS, HISTONE H2A, COMPLEX, BMI-1, CHROMATIN, H3, UBIQUITYLATION