Identification, cloning, expression, and biochemical characterization of the testis-specific RNA polymerase II elongation factor ELL3

The human ELL gene, which is a frequent target for translocation in acute myeloid leukemia, was initially isolated from rat liver nuclei and found to be an RNA polymerase II elongation factor. Based on homology to ELL, we later cloned ELL2 and demonstrated that it can also increase the catalytic rate of transcription elongation by RNA polymerase II. To better understand the role of ELL proteins in the regulation of transcription by RNA polymerase II, we have initiated a search for proteins related to ELLs. In this report, we describe the molecular cloning, expression, and characterization of ELL3, a novel RNA polymerase II elongation factor approximately 50% similar to both ELL and ELL2. Our transcriptional studies have demonstrated that ELL3 can also increase the catalytic rate of transcription elongation by RNA polymerase II. The C-terminal domain of ELL, which we recently demonstrated to be required and sufficient for the immortalization of myeloid progenitor cells, shares strong similarities to the C-terminal domain of ELL3. ELL3 was localized by immunofluorescence to the nucleus of cells, and Northern analysis indicated that ELL3 is a testis-specific RNA polymerase II elongation factor.