Abstract
Ikaros DNA binding factor plays critical roles in lymphocyte development. Changes in Ikaros expression levels during lymphopoiesis are controlled by redundant but also unique regulatory elements of its locus that are critical for this developmental process. We have recently shown that Ikaros binds its own locus in thymocytes in vivo. Here, we evaluated the role of an Ikaros binding site within its major lympho-myeloid promoter. We identified an Ikaros/Ets binding site within a promoter sub-region that was highly conserved in mouse and human. Deletion of this binding site increased the percentage of the reporter-expressing mouse lines, indicating that its loss provided a more permissive chromatin environment. However, once transcription was established, the lack of this site decreased transcriptional activity. These findings implicate a dual role for Ikaros/Ets1 binding on Ikzf1 expression that is exerted at least through its promoter.
Highlights
Accepted: June 3, 2015Published: July 2, 2015
The animal protocol was approved by the Subcommittee on Research Animal Care (SAC) of the Massachusetts General Hospital (MGH), which serves as the Institutional Animal Care and Use Committee (IACUC)
Changes in Ikaros expression correlate with its critical roles at various stages of lymphopoiesis
Summary
The Ikaros family of Kruppel-type zinc (Zn)-finger DNA-binding proteins are critical regulators for lymphocyte differentiation and homeostasis [1,2,3] They associate with the Nucleosome Remodeling Histone Deacetylace (NuRD) complex in the nucleus [4,5] to affect both gene activation and repression in hematopoietic cells [6,7,8,9,10,11]. Up-stream hemo-lymphoid specific trans-factors that bind the Ikzf locus in vivo have been identified in hematopoietic lineages [30], the actual roles of these factors on Ikzf regulation remain unknown One of these factors is Ikaros itself, suggesting an auto-regulatory function of the locus [30]. Our results implicate that Ikaros and/or Ets play a role in both repression and activation of Ikzf expression through its promoter element
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