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Dynamic control of the T-cell specification gene regulatory network

Rothenberg, Ellen V. (2019) Dynamic control of the T-cell specification gene regulatory network. Current Opinion in Systems Biology, 18 . pp. 62-76. ISSN 2452-3100. PMCID PMC7015151. doi:10.1016/j.coisb.2019.10.012.

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Specification of multipotent blood precursor cells in postnatal mice to become committed T-cell precursors involves a gene regulatory network of several interacting but functionally distinct modules. Many links of this network have been defined by perturbation tests and by functional genomics. However, using the network model to predict real-life kinetics of the commitment process is still difficult, partly due to the tenacity of repressive chromatin states, and to the ability of transcription factors to affect each other’s binding site choices through competitive recruitment to alternative sites (“coregulator theft”). To predict kinetics, future models will need to incorporate mechanistic information about chromatin state change dynamics and more sophisticated understanding of the proteomics and cooperative DNA site choices of transcription factor complexes.

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Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2019 Elsevier Ltd. Received 1 September 2019, Accepted 30 October 2019, Available online 6 November 2019. I am indebted to William J. R. Longabaugh for partnership in developing the 2017 version of the gene network model, and to Michael B. Elowitz, Carsten Peterson, Denis Thieffry, Hao Yuan Kueh, Hiroyuki Hosokawa, Jonas Ungerbäck, Mary A. Yui, and the late Eric H. Davidson for discussions that shaped the perspectives presented here. I apologize to many colleagues whose work was not cited in this short review. Relevant work in the author's lab has been supported by USPHS grants R01AI095943, R01AI135200, R01HD076915, and R01HL119102, and I gratefully acknowledge support from the Albert Billings Ruddock Professorship of Biology. Author contributions: EVR wrote the manuscript. Conflict of interest statement: Nothing declared.
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Albert Billings Ruddock ProfessorshipUNSPECIFIED
Subject Keywords:Gene regulatory network; Transcription factors; Notch signaling; Functional genomics; Epigenetic constraints; System dynamics; Topological model; T cell development
PubMed Central ID:PMC7015151
Record Number:CaltechAUTHORS:20191106-101546926
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Official Citation:Ellen V. Rothenberg, Dynamic control of the T-cell specification gene regulatory network, Current Opinion in Systems Biology, Volume 18, 2019, Pages 62-76, ISSN 2452-3100,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99691
Deposited By: Tony Diaz
Deposited On:06 Nov 2019 18:23
Last Modified:16 Feb 2022 18:01

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