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 Hess, Robert K. Slany

Research output: Contribution to journalArticle

26 Citations (Scopus)

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

Fingerprint

Polycomb Repressive Complex 1
Dimerization
Elongation
Cells
Genes
Proteins
Scaffolds
Machinery
Assays
Fusion reactions
Association reactions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Maethner, E., Garcia-Cuellar, M. P., Breitinger, C., Takacova, S., Divoky, V., Hess, J., & Slany, R. K. (2013). MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells. Cell Reports, 3(5), 1553-1566. https://doi.org/10.1016/j.celrep.2013.03.038

MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells. / Maethner, Emanuel; Garcia-Cuellar, Maria Paz; Breitinger, Constanze; Takacova, Sylvia; Divoky, Vladimir; Hess, Jay; Slany, Robert K.

In: Cell Reports, Vol. 3, No. 5, 30.05.2013, p. 1553-1566.

Research output: Contribution to journalArticle

Maethner, E, Garcia-Cuellar, MP, Breitinger, C, Takacova, S, Divoky, V, Hess, J & Slany, RK 2013, 'MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells', Cell Reports, vol. 3, no. 5, pp. 1553-1566. https://doi.org/10.1016/j.celrep.2013.03.038
Maethner, Emanuel ; Garcia-Cuellar, Maria Paz ; Breitinger, Constanze ; Takacova, Sylvia ; Divoky, Vladimir ; Hess, Jay ; Slany, Robert K. / MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells. In: Cell Reports. 2013 ; Vol. 3, No. 5. pp. 1553-1566.
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