Caballero, RosaliaSetien, FernandoLopez-Serra, LidiaBoix-Chornet, ManuelFraga, Mario FRopero, SantiagoMegias, DiegoAlaminos, MiguelSanchez-Tapia, Eva MMontoya, Maria CEsteller, ManelGonzalez-Sarmiento, RogelioBallestar, Esteban2012-11-092012-11-092007-08-01Caballero R, Setien F, Lopez-Serra L, Boix-Chornet M, Fraga MF, Ropero S, et al. Combinatorial effects of splice variants modulate function of Aiolos. J. Cell. Sci.. 2007 Aug; 120(Pt 15):2619-300021-9533http://hdl.handle.net/10668/612Journal Article; Research Support, Non-U.S. Gov't;The transcription factor Aiolos (also known as IKZF3), a member of the Ikaros family of zinc-finger proteins, plays an important role in the control of B lymphocyte differentiation and proliferation. Previously, multiple isoforms of Ikaros family members arising from differential splicing have been described and we now report a number of novel isoforms of Aiolos. It has been demonstrated that full-length Ikaros family isoforms localize to heterochromatin and that they can associate with complexes containing histone deacetylase (HDAC). In this study, for the first time we directly investigate the cellular localization of various Aiolos isoforms, their ability to heterodimerize with Ikaros and associate with HDAC-containing complexes, and the effects on histone modification and binding to putative targets. Our work demonstrates that the cellular activities of Aiolos isoforms are dependent on combinations of various functional domains arising from the differential splicing of mRNA transcripts. These data support the general principle that the function of an individual protein is modulated through alternative splicing, and highlight a number of potential implications for Aiolos in normal and aberrant lymphocyte function.enEmpalme AlternativoAnimalesLinfocitos BLínea CelularLínea Celular TumoralDimerizaciónRegulación de la Expresión GénicaHistona DesacetilasasHistonasHumanosFactor de Transcripción IkarosIsoformas de ProteínasFactores de TranscripciónDedos de ZincAiolosChromatinEpigeneticsIkarosIsoformsMi-2/NuRDMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Cells::Antibody-Producing Cells::B-LymphocytesMedical Subject Headings::Phenomena and Processes::Physiological PhenomenaMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured::Cell Line, TumorMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::DimerizationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::Histone DeacetylasesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::HistonesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Kruppel-Like Transcription Factors::Ikaros Transcription FactorMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein IsoformsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription FactorsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein Conformation::Protein Structure, Secondary::Amino Acid Motifs::Zinc FingersMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::RNA Processing, Post-Transcriptional::RNA Splicing::Alternative Splicingresearch article17646674open access10.1242/jcs.007344