STRUCTURE AND FUNCTION OF RNA-POLYMERASE-II ELONGATION-FACTOR ELL - IDENTIFICATION OF 2 OVERLAPPING ELL FUNCTIONAL DOMAINS THAT GOVERN ITS INTERACTION WITH POLYMERASE AND THE TERNARY ELONGATION COMPLEX

The human ELL gene on chromosome 19p13.1 undergoes frequent translocat ions with the trithorax-like MLL gene on chromosome 11q23 in acute mye loid leukemia, Recently, the human ELL gene was shown to encode an RNA polymerase II elongation factor that activates elongation by suppress ing transient pausing by polymerase at many sites along the DNA. In th is report, we identify and characterize two overlapping ELL functional domains that govern its interaction with RNA polymerase II and the te rnary elongation complex. Our findings reveal that, in addition to its elongation activation domain, ELL contains a novel type of RNA polyme rase II interaction domain that is capable of negatively regulating po lymerase activity in promoter-specific transcription initiation in vit ro. Notably, the MLL-ELL translocation results in deletion of a portio n of this functional domain, and ELL mutants lacking sequences deleted by the translocation bind RNA polymerase II and are fully active in e longation, but fail to inhibit initiation. Taken together, these resul ts raise the possibility that the MLL-ELL translocation could alter EL L-RNA polymerase II interactions that are not involved in regulation o f elongation.