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The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology. (Author #45)
Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology. (Author #52)ORCID iD: 0000-0003-0528-9782
Linköping University, Department of Physics, Chemistry and Biology, Computational Biology . Linköping University, The Institute of Technology. (Author #124)
2009 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 41, 553-562 p.Article in journal (Refereed) Published
Abstract [en]

Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.

Place, publisher, year, edition, pages
2009. Vol. 41, 553-562 p.
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Medical and Health Sciences
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URN: urn:nbn:se:liu:diva-18305DOI: 10.1038/ng.375OAI: oai:DiVA.org:liu-18305DiVA: diva2:217886
Available from: 2009-05-18 Created: 2009-05-18 Last updated: 2017-12-13Bibliographically approved

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Gustafsson, MikaHörnquist, MichaelTegnér, Jesper

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