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Epigenetic Dynamics in the Function of T-Lineage Regulatory Factor Bcl11b

Sidwell, Tom and Rothenberg, Ellen V. (2021) Epigenetic Dynamics in the Function of T-Lineage Regulatory Factor Bcl11b. Frontiers in Immunology, 12 . Art. No. 669498. ISSN 1664-3224. PMCID PMC8079813. doi:10.3389/fimmu.2021.669498.

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The transcription factor Bcl11b is critically required to support the development of diverse cell types, including T lymphocytes, type 2 innate lymphoid cells, neurons, craniofacial mesenchyme and keratinocytes. Although in T cell development its onset of expression is tightly linked to T-lymphoid lineage commitment, the Bcl11b protein in fact regulates substantially different sets of genes in different lymphocyte populations, playing strongly context-dependent roles. Somewhat unusually for lineage-defining transcription factors with site-specific DNA binding activity, much of the reported chromatin binding of Bcl11b appears to be indirect, or guided in large part by interactions with other transcription factors. We describe evidence suggesting that a further way in which Bcl11b exerts such distinct stage-dependent functions is by nucleating changes in regional suites of epigenetic modifications through recruitment of multiple families of chromatin-modifying enzyme complexes. Herein we explore what is - and what remains to be - understood of the roles of Bcl11b, its cofactors, and how it modifies the epigenetic state of the cell to enforce its diverse set of context-specific transcriptional and developmental programs.

Item Type:Article
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Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2021 Sidwell and Rothenberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 18 February 2021; Accepted: 23 March 2021; Published: 14 April 2021. The authors gratefully acknowledge Dorina Avram, Mark Leid, Hiroyuki Hosokawa, Keji Zhao, Jinfang Zhu, Ichiro Taniuchi, Peng Li, Pentao Liu, Satoshi Hirose, Boyoung Shin, and members of the Rothenberg lab for helpful discussions. Relevant work in the Rothenberg group was supported by USPHS grants R01AI083514 and R01AI135200 to ER. ER also received support from the Albert Billings Ruddock Professorship at Caltech. Author Contributions: TS drafted the manuscript, generated the figures, and wrote the final text. ER edited the manuscript and co-wrote the final text. Both authors approved the submitted version. Conflict of Interest: ER is a member of the Scientific Advisory Board of Century Therapeutics and has served as Advisor or Consultant for Kite Pharma and A2 Biotherapeutics. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Albert Billings Ruddock ProfessorshipUNSPECIFIED
Subject Keywords:transcription factor, T cell development, context-dependent gene regulation, developmental lineage choice, Runx, chromatin state modulation, repression, chromatin looping
PubMed Central ID:PMC8079813
Record Number:CaltechAUTHORS:20210517-094542881
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Official Citation:Sidwell T and Rothenberg EV (2021) Epigenetic Dynamics in the Function of T-Lineage Regulatory Factor Bcl11b. Front. Immunol. 12:669498. doi: 10.3389/fimmu.2021.669498
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109145
Deposited By: Tony Diaz
Deposited On:17 May 2021 18:14
Last Modified:17 May 2021 18:14

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