Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia
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Sanda-2012-Core Transcriptional.pdf
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1.96 MB
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Author(s)
Sanda, Takaomi
Lawton, Lee N.
Barrasa, M. Inmaculada
Fan, Zi Peng
Kohlhammer, Holger
Gutierrez, Alejandro
Ma, Wenxue
Tatarek, Jessica
Ahn, Yebin
Kelliher, Michelle A.
Date Issued
August 2012
Journal
Cancer Cell
Publisher
Elsevier
Citation
Sanda, Takaomi, Lee N. Lawton, M. Inmaculada Barrasa, Zi Peng Fan, Holger Kohlhammer, Alejandro Gutierrez, Wenxue Ma, et al. “Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia.” Cancer Cell 22, no. 2 (August 2012): 209–221. © 2012 Elsevier Inc.
Version
Final published version
Abstract
The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. We show that TAL1 forms a positive interconnected autoregulatory loop with GATA3 and RUNX1 and that the TAL1 complex directly activates the MYB oncogene, forming a positive feed-forward regulatory loop that reinforces and stabilizes the TAL1-regulated oncogenic program. One of the critical downstream targets in this circuitry is the TRIB2 gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the survival of T-ALL cells.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.ccr.2012.06.007
