SLAMing transcription | Nature Chemical Biology

Access through your institution Buy or subscribe _Science_ https://doi.org/10.1126/science.aao2793 (2018) Deciphering direct transcriptional responses to cell perturbations is challenging

because of vast differences in mRNA and protein turnover. One method that can potentially address this concern is SLAM-seq, which enables the direct quantification of newly synthesized

mRNAs. In this approach, the nucleotide analog 4-thiouridine is incorporated during RNA synthesis and then alkylated by iodoacetamide, which can be detected by reverse-transcriptase-induced

thymine-to-cytosine changes in mRNA 3′-end sequencing. Muhar et al. applied SLAM-seq in combination with the auxin-inducible degradation system or small-molecule inhibition to determine

whether rapid loss of the transcriptional regulators MYC or BRD4 resulted in global or specific loss in downstream gene expression. Performing SLAM-seq following degradation or inhibition of

BRD4 revealed global downregulation of transcription owing to alterations in Pol II–mediated promoter-proximal pause release. In contrast, loss of MYC led to a selective decrease in

transcription of genes involved in protein and nucleotide synthesis. Taken together, the combination of SLAM-seq with small-molecule-mediated inhibition or degradation may provide an

effective approach to measure global and specific transcriptional responses to cellular perturbations. This is a preview of subscription content, access via your institution ACCESS OPTIONS

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Contact customer support AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Chemical Biology https://www.nature.com/nchembio Grant Miura Authors * Grant Miura View author publications You

can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Grant Miura. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Miura, G. SLAMing transcription. _Nat Chem Biol_ 14, 525 (2018). https://doi.org/10.1038/s41589-018-0074-8 Download citation * Published: 16 May 2018 * Issue Date: June 2018 * DOI:

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