Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells

Networks of transcription factors (TFs) are thought to determine and maintain the identity of cells. Here we systematically repressed each of 100 TFs with shRNA and carried out global gene expression profiling in mouse embryonic stem (ES) cells. Unexpectedly, only the repression of a handful of TFs...

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Published in:Scientific reports Vol. 3; no. 1; p. 1390
Main Authors: Nishiyama, Akira, Sharov, Alexei A., Piao, Yulan, Amano, Misa, Amano, Tomokazu, Hoang, Hien G., Binder, Bernard Y., Tapnio, Richard, Bassey, Uwem, Malinou, Justin N., Correa-Cerro, Lina S., Yu, Hong, Xin, Li, Meyers, Emily, Zalzman, Michal, Nakatake, Yuhki, Stagg, Carole, Sharova, Lioudmila, Qian, Yong, Dudekula, Dawood, Sheer, Sarah, Cadet, Jean S., Hirata, Tetsuya, Yang, Hsih-Te, Goldberg, Ilya, Evans, Michele K., Longo, Dan L., Schlessinger, David, Ko, Minoru S. H.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 06.03.2013
Nature Publishing Group
Subjects:
631/114/2114
631/136/142
631/208/199
631/532/2117
Animals
Cell differentiation
Cluster Analysis
Embryonic Stem Cells - metabolism
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Silencing
Humanities and Social Sciences
Mice
Models, Biological
multidisciplinary
Oct-4 protein
Pluripotency
RNA Interference
Science
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptome
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Networks of transcription factors (TFs) are thought to determine and maintain the identity of cells. Here we systematically repressed each of 100 TFs with shRNA and carried out global gene expression profiling in mouse embryonic stem (ES) cells. Unexpectedly, only the repression of a handful of TFs significantly affected transcriptomes, which changed in two directions/trajectories: one trajectory by the repression of either Pou5f1 or Sox2 ; the other trajectory by the repression of either Esrrb , Sall4 , Nanog , or Tcfap4 . The data suggest that the trajectories of gene expression change are already preconfigured by the gene regulatory network and roughly correspond to extraembryonic and embryonic fates of cell differentiation, respectively. These data also indicate the robustness of the pluripotency gene network, as the transient repression of most TFs did not alter the transcriptomes.
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ISSN:2045-2322
2045-2322
DOI:10.1038/srep01390