Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding

Journal article

We report a novel variant in IKZF1 associated with IKAROS haploinsufficiency in a patient with familial immune thrombocytopenia (ITP). IKAROS, encoded by the IKZF1 gene, is a hematopoietic zinc-finger transcription factor that can directly bind to DNA. We show that the identified IKZF1 variant (p.His195Arg) alters a completely conserved histidine residue required for the folding of the third zinc-finger of IKAROS protein, leading to a loss of characteristic immunofluorescence nuclear staining pattern. In our case, genetic testing was essential for the diagnosis of IKAROS haploinsufficiency, of which known presentations include infections, aberrant hematopoiesis, leukemia, and age-related decrease in humoral immunity. Our family study underscores that, after infections, ITP is the second most common clinical manifestation of IKAROS haploinsufficiency

Authors: Cobb, BS; Morales-Alcelay, S; Kleiger, G; Brown, KE; Fisher, AG

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cold Spring Harbor Laboratory Press
• Journal: Genes & Development
• Volume: 14
• Issue: 17
• Pages: 2146-2160
• Publication date: 2000-09-01
• DOI: 10.1101/gad.816400
• EISSN: 1549-5477
• ISSN: 0890-9369
• Language: English
• Keywords: DNA-binding protein; Cell biology; Zinc finger; DNA; DNA-binding domain; Ectopic expression; Transcription factor; Leucine zipper; Biology; Chromatin; Gene; Molecular biology; Plasma protein binding; Heterochromatin; Genetics