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MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells
- Source :
- Cell Reports; May 2013, Vol. 3 Issue: 5 p1553-1566, 14p
- Publication Year :
- 2013
-
Abstract
- Stimulation of transcriptional elongation is a key activity of leukemogenic MLL fusion proteins. Here, we provide evidence that MLL-ENL also inhibits Polycomb-mediated silencing as a prerequisite for efficient transformation. Biochemical studies identified ENL as a scaffold that contacted the elongation machinery as well as the Polycomb repressive complex 1 (PRC1) component CBX8. These interactions were mutually exclusive in vitro, corresponding to an antagonistic behavior of MLL-ENL and CBX8 in vivo. CBX8 inhibited elongation in a specific reporter assay, and this effect was neutralized by direct association with ENL. Correspondingly, CBX8-binding-defective MLL-ENL could not fully activate gene loci necessary for transformation. Finally, we demonstrate dimerization of MLL-ENL as a neomorphic activity that may augment Polycomb inhibition and transformation.
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 3
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Cell Reports
- Publication Type :
- Periodical
- Accession number :
- ejs30514246
- Full Text :
- https://doi.org/10.1016/j.celrep.2013.03.038