Molecular characterization of Helios gene isoforms
Valeriano López-Segura
Eva María Sánchez TapiaThe Ikaros gene family is a group of transcriptional factors (Ikaros, Helios, Aiolos, Eos y Pegasus) which play an important role in lymphoid development. Besides acting as a classic transcriptional factor, this proteins also are involved in chromatin remodelling complexes. This gene family encodes zinc finger DNA-binding proteins. All the members of Ikaros family produce multiple isoforms via alternative mRNA splicing. Some of them are dominant-negative isoforms with a non functional DNA-binding domain. Those isoforms have been found in patients with acute lymphoblastic leukemia and may have a role in the development of leukemias or lymphomas. However, some of this dominant-negative isoforms are also found in healthy people. Our group have characterized new Helios isoforms in haematopoietic and non haematopoietic cellular lines. Several of this new isoforms have novel alternatives exons located in differents introns (He.1+2a,He.1+3a,He.1+5a), Moreover we have cloned isoforms that present a criptic process site in the exón 3 (He.1v y He.6v) and a new dominat-negative isoforma named He.S, which is generated by a novel splicing mechanism. We have studied the intracellular localization and the protein-protein interaction of some of these isoforms. Moreover, we have analized the Histones acetilation status. Our results suggest that He.1v plays an important role in the histones acetilation, specifically in the Histone H3 and confirms that this proteins are involved in remodelling complexes. The comparative study of differents isoforms will allow us to know more about the role of this family in normal lymphoid development and its possible implication in tumor development.