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Transcriptional cross-regulation of the RNA polymerase II elongation factor ELL by MLL-ELL fusion and HTLV-1 tax oncoproteins

Tuesday, October 25, 2011 — Poster Session II

Noon – 2:00 p.m.

Natcher Conference Center



* FARE Award Winner


  • TD Fufa
  • JS Byun
  • C Wakano
  • CM Haggerty
  • K Gardner


The mammalian eleven-nineteen lysine-rich leukemia gene (ELL) encodes an RNA polymerase II (Pol II) transcription elongation factor that frequently participates in leukemogenic chromosomal translocations involving the mixed-lineage leukemia gene (MLL). However, the mechanisms underlying ELL function and its contribution to the progression of leukemia remain unclear. Here, we describe ELL as a regulatory mechanism through which leukemogenic chromosomal translocations and viral accessory proteins commandeer and usurp multiple phases of the transcription cycle. By employing combinations of gene depletion, subcellular localization, immunopurification and genome location analyses we reveal that ELL bridges dynamic interactions that define two distinct rate-limiting steps in transcription: 1) early targeting and stabilization of the pre-initiation complex containing Pol II and the histone acetyltransferase p300, and 2) stabilization and recruitment of additional elongation factors including the positive transcription elongation factor b (P-TEFb), the MLL-fusion partner AFF4 and the Pol II associated factor 1 (PAF1). Furthermore, we show that ELL is a shared transcriptional target of both MLL-ELL fusion and the human T cell leukemia virus type I (HTLV-1) Tax oncoproteins. This elucidation of ELL function as a common cellular target of multiple leukemogenic disease processes strongly implicates ELL as potential candidate for targeted therapy in hematopoietic malignancies.

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