MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells

Emanuel Maethner, Maria Paz Garcia-Cuellar, Constanze Breitinger, Sylvia Takacova, Vladimir Divoky, Jay L. Hess, Robert K. Slany

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 invitro, corresponding to an antagonistic behavior of MLL-ENL and CBX8 invivo. 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.

Original languageEnglish (US)
Pages (from-to)1553-1566
Number of pages14
JournalCell Reports
Volume3
Issue number5
DOIs
StatePublished - May 30 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells'. Together they form a unique fingerprint.

Cite this