Discovery

Ikzf2, encoding the protein Helios, belongs to the Ikaros family of zinc finger (ZnF) transcription factors. It was discovered by two different groups in 1998, as a gene homologous to Ikaros (encoded by Ikzf1) [Hahm et al., Genes Dev., 1998; Kelley et al., Curr Biol, 1998].

Expression

Helios is expressed in the hematopoietic system, in various developmental stages and cell lineages of blood cells. It is expressed in developing T-cells, and it is to date most highly studied in the T-cell lineage.

Disease relevance of Ikzf2

• These results do not suggest any obvious contribution of Helios or Aiolos to oncogenesis of the mouse thymic lymphomas [1].
• Although expression of the DNA-binding mutant of Helios did not contribute to developmental abnormalities at early times after transplantation, 60% of animals that expressed the Helios DNA-binding mutant developed an aggressive and transplantable T-cell lymphoma 4 to 10 months after transplantation [2].

High impact information on Ikzf2

• Unlike the B cell results, however, only a fraction of the Ikaros, presumably the fraction associated with Helios, exhibited centromeric localization in T cells [3].
• Although Ikaros is present in most hematopoietic cells, Helios was found primarily in T cells [3].
• Helios, a member of the Ikaros family of DNA-binding proteins, is expressed in multipotential lymphoid progenitors and throughout the T lineage [4].
• Further evidence that ectopic Helios expression contributes to B cell abnormalities was provided by the observation that Helios transgenic mice developed metastatic lymphoma as they aged [4].
• To test this possibility, transgenic mice were generated that express Helios under the control of an Ig mu enhancer [4].

Biological context of Ikzf2

• Analysis using polymorphic markers around the two regions revealed that neither locus exhibited allelic loss in the 78 lymphomas that were induced in p53 wild-type mice, whereas in 102 p53(KO / + ) mouse-derived lymphomas Helios and Aiolos loci showed allelic loss in 8% (8 / 102) and 33% (34 / 102), respectively [1].
• Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors [5].
• The preferential expression of Helios in the earliest stages of hematopoiesis suggests that this gene functions predominantly in early progenitors [5].
• Analysis of the primary sequences of Helios, Ikaros and Aiolos revealed that the DNA-binding, transcriptional activation and dimerization domains are functionally conserved [5].
• To evaluate the role of Helios in avian haemato/lymphopoiesis, we have characterized the avian Helios gene [6].

Anatomical context of Ikzf2

• Expression of Helios was detected in the earliest hematopoietic sites of the embryo, in hematopoietic stem cells in the adult and was subsequently restricted to a subset of cells in the T cell lineage [5].
• Commitment to the B cell lineage was unaltered in Helios transgenic mice, and numbers of surface IgM(+) B cells were normal in the bone marrow and spleen [4].
• Additionally, expression in the bursa of Fabricius, germinal centres and B-cell lines suggests a role for Helios also in the B-cell lineage [6].
• Abstract Helios (Znfn1a2) is an Ikaros-related lymphoid regulatory protein with possible involvement in T-cell development and function as well as in the early events of haematopoietic stem cell differentiation [6].

References