The BTB-ZF Family of Transcription Factors: Key Regulators of Lineage Commitment and Effector Function Development in the Immune System

Beaulieu, Aimee M.; Sant’Angelo, Derek B.

doi:10.4049/jimmunol.1004006

Cited by 81 publications

(81 citation statements)

References 100 publications

(122 reference statements)

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“…While it could conceivably be beneficial for these cells to maintain helper-cytotoxic bipotency, we show that restraining Runx3 expression is essential to preserve IL-4 production potential. Future studies will determine if the distinctive functions of Thpok and LRF result from intrinsic differences in their biochemical activities, for instance the recruitment of co-repressor molecules (Beaulieu and Sant'Angelo, 2011), or from their different levels or patterns of expression.…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell Differentiation

et al. 2012

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Summary T helper (Th) cells are critical for defenses against infection and recognize peptides bound to Class II Major Histocompatibility Complex (MHC-II) molecules. Although transcription factors have been identified that direct helper cells into specific effector fates, whether a ‘master’ regulator controls the developmental program common to all Th cells remains unclear. Here we showed that the two transcription factors Thpok and LRF share this function. Although disruption of both factors did not prevent the generation of MHC II-specific T cells, these cells failed to express Th cell genes or undergo Th cell differentiation in vivo. In contrast, T cells lacking Thpok only displayed LRF-dependent functions and contributed to multiple effector responses, both in vitro and in vivo, with the notable exception of Th2 cell responses that control extra-cellular parasites. These findings identify the Thpok-LRF pair as a core node of Th cell differentiation and function.

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Section: Discussionmentioning

confidence: 99%

The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell Differentiation

et al. 2012

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“…POK proteins have been implicated in many biological processes, including B-cell fate determination and cell cycle progression. Consequently, dysfunction of POK proteins has been involved in tumorigenesis and developmental disorders (10,30). However, few POK proteins were reported to function in immune response, especially in innate immune response.…”

Section: Discussionmentioning

confidence: 99%

Zinc finger protein ZBTB20 promotes toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription

Liu

Zhang

Bao

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Toll-like receptor (TLR) signaling is critical in innate response against invading pathogens. However, the molecular mechanisms for full activation of TLR-triggered innate immunity need to be fully elucidated. The broad complex tramtrack bric-a-brac/poxvirus and zinc finger (BTB/POZ) family is a class of transcription factors involved in many biological processes. However, few BTB/POZ proteins were reported to function in innate immune response. Zinc finger and BTB domain-containing 20 (ZBTB20), a member of BTB/POZ family, functions in neurogenesis and represses α-fetoprotein gene transcription in liver. However, the immunological functions of ZBTB20 remain unknown. Here, we found that myeloid cellspecific ZBTB20 KO mice were resistant to endotoxin shock and Escherichia coli-caused sepsis. ZBTB20 deficiency attenuated TLRtriggered production of proinflammatory cytokines and type I IFN in macrophages, which attributed to higher abundance of IκBα protein and impaired activity of NF-κB. Furthermore, ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription.

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“…Bcl-6 is a member of the broad-complex, tramtrack and bric-à-brac-zinc finger (BTB-ZF) family of proteins, and has been identified as a lineage-defining transcription factor required for both T FH cell differentiation and the formation of germinal centers (9-13). Additionally, Bcl-6 is important to numerous aspects of B cell development and function, as well as the differentiation of CD4 + and CD8 + memory T cell populations (5, 14-16).…”

Section: Introductionmentioning

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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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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The BTB-ZF Family of Transcription Factors: Key Regulators of Lineage Commitment and Effector Function Development in the Immune System

Cited by 81 publications

References 100 publications

The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell Differentiation

The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell Differentiation

Zinc finger protein ZBTB20 promotes toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription

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

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