The Ikaros family in lymphocyte development

Heizmann, Beate; Kastner, Philippe; Chan, Susan

doi:10.1016/j.coi.2017.11.005

Cited by 99 publications

(78 citation statements)

References 66 publications

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“…Helios ( Ikzf2 ) is a member of the Ikaros transcription factor family that is characterized by four highly conserved C2H2 zinc fingers involved in DNA binding and two C2H2 zinc fingers required for homodimeric and heterodimeric protein interactions with other family members (Fig. ) . There are five members of the Ikaros transcription factor family.…”

Section: The Ikaros Transcription Factor Familymentioning

confidence: 99%

“…There are five members of the Ikaros transcription factor family. The founding member, Ikaros ( Ikzf1 ), was first described in 1992 and the remaining four members of the family, Aiolos ( Ikzf3 ), Helios, Eos ( Ikzf4 ) and Pegasus ( Ikzf5 ) were cloned by the end of the decade . All members of the Ikaros family are expressed in the hematopoietic system, some widely and some more restricted.…”

Section: The Ikaros Transcription Factor Familymentioning

confidence: 99%

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Helios: still behind the clouds

Thornton

Shevach

2019

Immunology

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Regulatory T (Treg) cells are a subset of CD4 + T cells that are critical for the maintenance of self-tolerance. The forkhead box transcription factor Foxp3 is a master regulator for the Treg phenotype and function and its expression is essential in Treg cells, as the loss of Foxp3 results in lethal autoimmunity. Two major subsets of Treg cells have been described in vivo; thymus-derived Treg (tTreg) cells that develop in the thymus and peripherally induced Treg (pTreg) cells that are derived from conventional CD4 + Foxp3 À T cells and are converted in peripheral tissues to cells that express Foxp3 and acquire suppressive ability. The transcription factor Helios, a member of the Ikaros transcription factor family, is expressed in 60-70% of Treg cells in both mouse and man, and is believed to be a marker of tTreg cells. In this review, we discuss the role and function of Helios in Treg cells, the controversy surrounding the use of Helios as a marker of tTreg cells, and how Helios controls specific aspects of the Treg cell program.

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Section: The Ikaros Transcription Factor Familymentioning

confidence: 99%

Section: The Ikaros Transcription Factor Familymentioning

confidence: 99%

Helios: still behind the clouds

Thornton

Shevach

2019

Immunology

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“…One example is patients with heterozygous mutations in IKZF1, the gene encoding for the hematopoetic transcription factor IKAROS. 32 IKAROS-haploinsufficient patients present at any age with recurrent/severe bacterial infections as well as autoimmunity, including idiopathic thrombocytopenic purpura and systemic lupus erythematosus. 33 A unique and defining characteristic of this particular form of CVID is the progressive loss of immunoglobulins and peripheral B cells with age, a feature thought to be caused by premature stem cell senescence.…”

Section: Defects In B-cell Developmentmentioning

confidence: 99%

Birds of a feather

Romberg

Lawrence

2019

Annals of Allergy, Asthma & Immunology

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Common variable immune deficiency (CVID) is suggested by a clinical phenotype of infectious susceptibility, autoimmunity, and lymphoproliferation. A diagnosis is made with laboratory evidence of antibody failure. Genetic variants likely contributing to CVID can be identified in up to 30% of patients. Genetic mutations are enriched in patients with CVID with any of the following: early-onset manifestations, autoimmune or inflammatory complications, a family history of immunodeficiency, or low B-cell numbers. Identification of a mutation in a CVID-related gene can have direct prognostic and therapeutic implications.

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“…Ikaros family members, which have been shown to play critical roles in lymphocyte development , were the most abundantly represented family (Fig. 1D).…”

Section: Resultsmentioning

confidence: 99%

Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting

et al. 2019

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Secondary diversification of the Ig repertoire occurs through somatic hypermutation (SHM), gene conversion (GCV), and class switch recombination (CSR)—three processes that are initiated by activation‐induced cytidine deaminase (AID). AID targets Ig genes at orders of magnitude higher than the rest of the genome, but the basis for this specificity is poorly understood. We have previously demonstrated that enhancers and enhancer‐like sequences from Ig genes are capable of stimulating SHM of neighboring genes in a capacity distinct from their roles in increasing transcription. Here, we use an in vitro proteomics approach to identify E‐box, MEF2, Ets, and Ikaros transcription factor family members as potential binders of these enhancers. ChIP assays in the hypermutating Ramos B cell line confirmed that many of these factors bound the endogenous Igλ enhancer and/or the IgH intronic enhancer (Eμ) in vivo. Further investigation using SHM reporter assays identified binding sites for E2A and MEF2B in Eμ and demonstrated an association between loss of factor binding and decreases in the SHM stimulating activity of Eμ mutants. Our results provide novel insights into trans‐acting factors that dictate SHM targeting and link their activity to specific DNA binding sites within Ig enhancers.

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The Ikaros family in lymphocyte development

Cited by 99 publications

References 66 publications

Helios: still behind the clouds

Helios: still behind the clouds

Birds of a feather

Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting

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