Hosokawa, Hiroyuki and Ungerbäck, Jonas and Wang, Xun and Matsumoto, Masaki and Nakayama, Keiichi I. and Cohen, Sarah M. and Tanaka, Tomoaki and Rothenberg, Ellen V. (2018) Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding. Immunity, 48 (6). pp. 1119-1134. ISSN 1074-7613. PMCID PMC6063530; PMC6207499. doi:10.1016/j.immuni.2018.04.024. https://resolver.caltech.edu/CaltechAUTHORS:20180621-101905456
![[img]](https://authors.library.caltech.edu/style/images/fileicons/application_pdf.png)
![[img]](https://authors.library.caltech.edu/style/images/fileicons/application_vnd.ms-excel.png)
Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20180621-101905456
Abstract
Transcription factors normally regulate gene expression through their action at sites where they bind to DNA. However, the balance of activating and repressive functions that a transcription factor can mediate is not completely understood. Here, we showed that the transcription factor PU.1 regulated gene expression in early T cell development both by recruiting partner transcription factors to its own binding sites and by depleting them from the binding sites that they preferred when PU.1 was absent. The removal of partner factors Satb1 and Runx1 occurred primarily from sites where PU.1 itself did not bind. Genes linked to sites of partner factor “theft” were enriched for genes that PU.1 represses despite lack of binding, both in a model cell line system and in normal T cell development. Thus, system-level competitive recruitment dynamics permit PU.1 to affect gene expression both through its own target sites and through action at a distance.
| Item Type: | Article | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Related URLs: |
| ||||||||||||||||||||||||||
| ORCID: |
| ||||||||||||||||||||||||||
| Additional Information: | © 2018 Elsevier Inc. Received 19 October 2017, Revised 21 February 2018, Accepted 19 April 2018, Available online 19 June 2018. We thank Diana Perez, Jaime Tijerina, and Rochelle Diamond for cell sorting and advice, Ingrid Soto for mouse colony care, Vijaya Kumar for library preparation and sequencing, Henry Amrhein and Diane Trout for computational help, Igor Antoshechkin for sequencing management, and members of the Rothenberg group for valuable discussion and reagents. Fellowships from the Manpei Suzuki Diabetes Foundation (to H.H.) and from the Swedish Research Council (to J.U.) are gratefully acknowledged. This work was supported by grants from the USPHS to E.V.R. (R01HD076915 and R01AI95943) and Grants-in-Aid for Advanced Research and Development Programs for Medical Innovation, the Takeda Science Foundation, and SENSHINE Medical Research Foundation to T.T. This work was partly performed in the Collaborative Research Project Program of the Medical Institute of Bioregulation, Kyushu University, and was also supported by the L.A. Garfinkle Memorial Laboratory Fund and the Al Sherman Foundation, by funds from the Provost and Division of Biology & Biological Engineering of the California Institute of Technology, and by the Albert Billings Ruddock Professorship to E.V.R. Author Contributions: H.H., J.U., and E.V.R. designed the project, analyzed data, and wrote the manuscript. T.T. designed proteomic strategy, analyzed data, and reviewed the manuscript. H.H. and J.U. conducted most of the experiments. X.W. performed ATAC-seq experiments, S.M.C. performed Runx1DN experiments, and M.M., K.I.N., and T.T. conducted proteomic analysis. The authors declare no competing interests. | ||||||||||||||||||||||||||
| Errata: | The Cas9-GFP retroviral vector used for these studies was in the pQCXIN backbone, not in pMIG as originally stated. This error was inadvertent, and the correct information is now provided in the updated STAR Methods. The authors apologize for the error. | ||||||||||||||||||||||||||
| Funders: |
| ||||||||||||||||||||||||||
| Subject Keywords: | Spi1; Runx1; Satb1; DNA accessibility; repression | ||||||||||||||||||||||||||
| Issue or Number: | 6 | ||||||||||||||||||||||||||
| PubMed Central ID: | PMC6063530; PMC6207499 | ||||||||||||||||||||||||||
| DOI: | 10.1016/j.immuni.2018.04.024 | ||||||||||||||||||||||||||
| Record Number: | CaltechAUTHORS:20180621-101905456 | ||||||||||||||||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20180621-101905456 | ||||||||||||||||||||||||||
| Official Citation: | Hiroyuki Hosokawa, Jonas Ungerbäck, Xun Wang, Masaki Matsumoto, Keiichi I. Nakayama, Sarah M. Cohen, Tomoaki Tanaka, Ellen V. Rothenberg, Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding, Immunity, Volume 48, Issue 6, 19 June 2018, Pages 1119-1134.e7, ISSN 1074-7613, https://doi.org/10.1016/j.immuni.2018.04.024. (https://www.sciencedirect.com/science/article/pii/S1074761318301936) | ||||||||||||||||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||||||||||
| ID Code: | 87302 | ||||||||||||||||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||||||||||||||||
| Deposited By: | Tony Diaz | ||||||||||||||||||||||||||
| Deposited On: | 21 Jun 2018 17:42 | ||||||||||||||||||||||||||
| Last Modified: | 01 Jun 2023 22:39 |
Repository Staff Only: item control page
