A high-resolution map of transcriptional repression
Ferreirós Vidal, I
eLife Sciences Publications
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Liang, Z., Brown, K., Carroll, T., Taylor, B., Ferreirós Vidal, I., Hendrich, B., Rueda, D., et al. (2017). A high-resolution map of transcriptional repression. eLife, 6 (e22767)https://doi.org/10.7554/eLife.22767
Turning genes on and off is essential for development and homeostasis, yet little is known about the sequence and causal role of chromatin state changes during the repression of active genes. This is surprising, as defective gene silencing underlies developmental abnormalities and disease. Here we delineate the sequence and functional contribution of transcriptional repression mechanisms at high temporal resolution. Inducible entry of the NuRD-interacting transcriptional regulator Ikaros into mouse pre-B cell nuclei triggered immediate binding to target gene promoters. Rapid RNAP2 eviction, transcriptional shutdown, nucleosome invasion, and reduced transcriptional activator binding required chromatin remodeling by NuRD-associated Mi2beta/CHD4, but were independent of HDAC activity. Histone deacetylation occurred after transcriptional repression. Nevertheless, HDAC activity contributed to stable gene silencing. Hence, high resolution mapping of transcriptional repression reveals complex and interdependent mechanisms that underpin rapid transitions between transcriptional states, and elucidates the temporal order, functional role and mechanistic separation of NuRD-associated enzymatic activities.
genes and chromosomes, B cell, corepressor complex, gene silencing, Ikaros, mouse, transcriptional repression
This work was funded by the Medical Research Council UK, Wellcome, and UK-China Scholarships for Excellence (a scheme run jointly by the Department for Business, Innovation and Skills and the China Scholarship Council).
Wellcome Trust (098021/Z/11/Z)
External DOI: https://doi.org/10.7554/eLife.22767
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264541
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International