IKAROS: a multifunctional regulator of the polymerase II transcription cycle

Bottardi, Stefania; Mavoungou, Lionel; Milot, Éric

doi:10.1016/j.tig.2015.05.003

Cited by 24 publications

(19 citation statements)

References 122 publications

(179 reference statements)

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“…Another – non-mutually exclusive – possibility may be that Aiolos and Ikaros association with the Bcl6 promoter near the TSS contributes to the assembly and/or activation of the transcriptional initiation complex. In this regard, Ikaros has been shown to physically interact with, and alter the activity of, the RNA Pol II complex (64). It is also possible that Aiolos and Ikaros may be required to mediate interactions between the Bcl6 promoter and distal enhancers.…”

Section: Discussionmentioning

confidence: 99%

Integrated STAT3 and Ikaros Zinc Finger Transcription Factor Activities Regulate Bcl-6 Expression in CD4+ Th Cells

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Baker

et al. 2017

The Journal of Immunology

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Bcl-6 (B cell lymphoma-6) is a transcriptional repressor required for the differentiation of T follicular helper (TFH) cell populations. Currently, the molecular mechanisms underlying the transcriptional regulation of Bcl-6 expression are unclear. Here, we have identified the Ikaros zinc finger (IkZF) transcription factors Aiolos and Ikaros as novel regulators of Bcl-6. We found that increased expression of Bcl-6 in CD4+ T helper cell populations correlated with enhanced enrichment of Aiolos and Ikaros at the Bcl6 promoter. Furthermore, overexpression of Aiolos or Ikaros, but not the related family member Eos, was sufficient to induce Bcl6 promoter activity. Intriguingly, STAT3, a known Bcl-6 transcriptional regulator, physically interacted with Aiolos to form a transcription factor complex capable of inducing the expression of Bcl6 and the TFH-associated cytokine receptor Il6ra. Importantly, in vivo studies revealed that the expression of Aiolos was elevated in antigen-specific TFH cells compared to that observed in non-TFH effector T helper cells generated in response to influenza infection. Collectively, these data describe a novel regulatory mechanism wherein STAT3 and the IkZF transcription factors Aiolos and Ikaros cooperate to regulate Bcl-6 expression.

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Section: Discussionmentioning

confidence: 99%

Integrated STAT3 and Ikaros Zinc Finger Transcription Factor Activities Regulate Bcl-6 Expression in CD4+ Th Cells

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Powell

Baker

et al. 2017

The Journal of Immunology

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“…Despite its functional importance, DRD1 is unlikely the only chromatin remodeler participating in the transcription process. In animals, different CHD proteins are required at the initiation, elongation, or termination phase of Pol II transcription [72, 73], indicating that their heterogeneous biochemical activities suit multiple aspects of the transcription cycle. The different effects of PKL and DRD1 on DNA methylation suggest they could function in different phases of Pol V transcription [56].…”

Section: Discussionmentioning

confidence: 99%

The developmental regulator PKL is required to maintain correct DNA methylation patterns at RNA-directed DNA methylation loci

et al. 2017

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BackgroundThe chromodomain helicase DNA-binding family of ATP-dependent chromatin remodeling factors play essential roles during eukaryote growth and development. They are recruited by specific transcription factors and regulate the expression of developmentally important genes. Here, we describe an unexpected role in non-coding RNA-directed DNA methylation in Arabidopsis thaliana.ResultsThrough forward genetic screens we identified PKL, a gene required for developmental regulation in plants, as a factor promoting transcriptional silencing at the transgenic RD29A promoter. Mutation of PKL results in DNA methylation changes at more than half of the loci that are targeted by RNA-directed DNA methylation (RdDM). A small number of transposable elements and genes had reduced DNA methylation correlated with derepression in the pkl mutant, though for the majority, decreases in DNA methylation are not sufficient to cause release of silencing. The changes in DNA methylation in the pkl mutant are positively correlated with changes in 24-nt siRNA levels. In addition, PKL is required for the accumulation of Pol V-dependent transcripts and for the positioning of Pol V-stabilized nucleosomes at several tested loci, indicating that RNA polymerase V-related functions are impaired in the pkl mutant.Conclusions PKL is required for transcriptional silencing and has significant effects on RdDM in plants. The changes in DNA methylation in the pkl mutant are correlated with changes in the non-coding RNAs produced by Pol IV and Pol V. We propose that at RdDM target regions, PKL may be required to create a chromatin environment that influences non-coding RNA production, DNA methylation, and transcriptional silencing.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1226-y) contains supplementary material, which is available to authorized users.

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“…This distinct structure confers diverse functional capabilities, as IkZF family members can both positively and negatively regulate gene expression through direct interactions with DNA, as well as by forming transcriptional complexes with other proteins. Mechanistically, IkZF factors have been shown to regulate gene expression by (i) remodeling chromatin structure through association with chromatin remodeling complexes such as the nucleosome remodeling deacetylase (NuRD), (ii) interacting with and promoting the activity of the RNA Pol II transcription initiation complex, and (iii) inducing chromosome conformational changes by mediating interactions between distal cis -regulatory regions (14, 15, 24–26).…”

Section: Introductionmentioning

confidence: 99%

Ikaros Zinc Finger Transcription Factors: Regulators of Cytokine Signaling Pathways and CD4+ T Helper Cell Differentiation

et al. 2019

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CD4 + T helper cells are capable of differentiating into a number of effector subsets that perform diverse functions during adaptive immune responses. The differentiation of each of these subsets is governed, in large part, by environmental cytokine signals and the subsequent activation of downstream, cell-intrinsic transcription factor networks. Ikaros zinc finger (IkZF) transcription factors are known regulators of immune cell development, including that of CD4 + T cell subsets. Over the past decade, members of the IkZF family have also been implicated in the differentiation and function of individual T helper cell subsets, including T helper 1 (T H 1), T H 2, T H 17, T follicular (T FH ), and T regulatory (T REG ) cells. Now, an increasing body of literature suggests that the distinct cell-specific cytokine environments responsible for the development of each subset result in differential expression of IkZF factors across T helper populations. Intriguingly, recent studies suggest that IkZF members influence T helper subset differentiation in a feed-forward fashion through the regulation of these same cytokine-signaling pathways. Here, we review the increasingly prominent role for IkZF transcription factors in the differentiation of effector CD4 + T helper cell subsets.

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IKAROS: a multifunctional regulator of the polymerase II transcription cycle

Cited by 24 publications

References 122 publications

Integrated STAT3 and Ikaros Zinc Finger Transcription Factor Activities Regulate Bcl-6 Expression in CD4+ Th Cells

Integrated STAT3 and Ikaros Zinc Finger Transcription Factor Activities Regulate Bcl-6 Expression in CD4+ Th Cells

The developmental regulator PKL is required to maintain correct DNA methylation patterns at RNA-directed DNA methylation loci

Ikaros Zinc Finger Transcription Factors: Regulators of Cytokine Signaling Pathways and CD4+ T Helper Cell Differentiation

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