Cm. Kelley et al., HELIOS, A NOVEL DIMERIZATION PARTNER OF IKAROS EXPRESSED IN THE EARLIEST HEMATOPOIETIC PROGENITORS, Current biology, 8(9), 1998, pp. 508-515
Background: Normal hematopoietic development depends on the activity o
f the Ikaros transcription factor, which contains distinct zinc-finger
domains that mediate DNA binding and protein dimerization. Mice homoz
ygous for a transgene encoding a dominant-negative version of Ikaros t
hat lacks the DNA-binding domain but not the dimerization domain have
a more severe phenotype than Ikaros null mice. This observation sugges
ts the presence of factor(s) that can dimerize with Ikaros and partial
ly complement its function. One previously identified factor, Aiolos,
probably serves this role in the lymphoid system; a related factor inv
olved in hematopoietic progenitors remains unknown, however. Results:
Here, we describe the cloning of an Ikaros-related gene, Hellos. Analy
sis of the primary sequences of Hellos, Ikaros and Aiolos revealed tha
t the DNA-binding, transcriptional activation and dimerization domains
are functionally conserved. Hellos activated transcription from Ikaro
s DNA-binding sites and could dimerize with itself, Ikaros or Aiolos.
Expression of Helios was detected in the earliest hematopoietic sites
of the embryo, in hematopoietic stem cells in the adult and was subseq
uently restricted to a subset of cells in the T cell lineage. Hellos c
o-localized with Ikaros and Aiolos proteins in macromolecular nuclear
structures and formed stable complexes in vivo with the dominant-negat
ive version of Ikaros. Conclusions: Distinct but overlapping expressio
n patterns of members of the Ikaros gene family during hematopoiesis m
ight result in the formation of different multimeric complexes that ha
ve specific roles in lineage progression. The preferential expression
of Hellos in the earliest stages of hematopoiesis suggests that this g
ene functions predominantly in early progenitors. (C) Current Biology
Ltd ISSN 0960-9822.