HGNC Approved Gene Symbol: EAF1
Cytogenetic location: 3p25.1 Genomic coordinates (GRCh38) : 3:15,427,598-15,442,613 (from NCBI)
By the yeast 2-hybrid method with the sequence of ELL (600284) as bait and by database searching, Simone et al. (2001) isolated a novel cDNA, which they termed ELL-associated factor-1 (EAF1), from a bone marrow cDNA library. The deduced 268-amino acid EAF1 protein contains a region rich in serine, aspartic acid, and glutamic acid residues in the C terminus that shares homology with the transcriptional activation domains of several translocation partner proteins of MLL (159555), including AF4 (159557) and LAF4 (601464). Northern blot analysis detected a 4.5-kb transcript in all tissues examined except thymus, which demonstrated only minimal expression. An additional approximately 2.0-kb transcript was detected in testis and skeletal muscle. Incubation of HeLa and 293 cells with EAF1 antibody demonstrated a speckled nuclear pattern in nondividing cells and a diffuse pattern in dividing cells.
Using specific antibodies, Simone et al. (2001) found that endogenous EAF1 and ELL proteins coimmunoprecipitated in multiple cell lines and form a stable complex. Endogenous EAF1 also exhibited the capacity to interact with ELL2 (601874). Simone et al. (2001) mapped the transcriptional activity of EAF1 to the C-terminal one-third of EAF1, which contains the region of homology to AF4 family members. By confocal microscopy, endogenous EAF1 and ELL colocalized in a distinct nuclear speckled pattern. Transfection of the MLL/ELL fusion gene delocalized EAF1 from its nuclear speckled distribution to a diffuse nucleoplasmic pattern. In leukemic cell lines derived from mice transplanted with MLL/ELL-transduced bone marrow, EAF1 speckles were not detected. Simone et al. (2001) suggested that expression of the MLL/ELL fusion protein may have a dominant effect on the normal protein-protein interactions of ELL.
Kong et al. (2005) found that human EAF1 and EAF2 (607659) interacted directly with ELL to form a stable complex that targeted the RNA polymerase II ternary elongation complex and strongly stimulated its overall rate of elongation.
The International Radiation Hybrid Mapping Consortium mapped the EAF1 gene to chromosome 3 (RH135807).
Kong, S. E., Banks, C. A. S., Shilatifard, A., Conaway, J. W., Conaway, R. C. ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL. Proc. Nat. Acad. Sci. 102: 10094-10098, 2005. [PubMed: 16006523] [Full Text: https://doi.org/10.1073/pnas.0503017102]
Simone, F., Polak, P. E., Kaberlein, J. J., Luo, R. T., Levitan, D. A., Thirman, M. J. EAF1, a novel ELL-associated factor that is delocalized by expression of the MLL-ELL fusion protein. Blood 98: 201-209, 2001. [PubMed: 11418481] [Full Text: https://doi.org/10.1182/blood.v98.1.201]