Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression

TEL is a transcriptional repressor that is a frequent target of chromosomal translocations in a large number of hematalogical malignancies. These rear rangements fuse a potent oligomerization module, the SAM domain of TEL, to a variety of tyrosine kinases or transcriptional regulatory proteins. The s elf-associating property of TEL-SAM is essential for cell transformation in many, if not all of these diseases. Here we show that the TEL-SAM domain f orms a helical, head-to-tail polymeric structure held together by strong in termolecular contacts, providing the first clear demonstration that SAM dom ains can polymerize. Our results also suggest a mechanism by which SAM doma ins could mediate the spreading of transcriptional repression complexes alo ng the chromosome.