University of Cambridge > > Genetics Seminar  >  Decoding Transcriptional Regulation and Kinetics Using Single-Cell Transcriptomics.

Decoding Transcriptional Regulation and Kinetics Using Single-Cell Transcriptomics.

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If you have a question about this talk, please contact Caroline Newnham.

Host: Michael Imbeault

The advancement of single-cell RNA -sequencing (scRNA-seq) has opened up for transcriptome-wide analyses of transcriptional regulation and dynamics. My lab developed full-length scRNA-seq protocols (e.g. Smart-seq2 and Smart-seq3) that we use to study patterns of gene expression and regulation at single cell resolution. We recently inferred transcriptional burst kinetics for thousands of endogenous genes using allele-resolved scRNA-seq, which revealed that core promoter elements and enhancers control burst size and frequency, respectively3. We have inferred allelic waiting times between consecutive bursts based on mRNA degradation rates that we are now comparing to direct readouts from 4sU-based labelling of newly transcribed RNAs in single cells4. Having transcriptome-wide readouts of bursting kinetics enables more detailed investigations into patterns of transcriptional dynamics in response to the perturbation of transcriptional regulators and co-factors, which we are actively pursuing. Moreover, we are exploring how human genetic variation affects bursting kinetics to be able to distinguish the contributions of specific DNA -binding proteins to either burst size or frequency mediated regulation. Altogether, transcriptome-wide single-cell measurements of gene expression enable quantitative investigation of the episodic transcription of our genes and opens up for mechanistic inquiries into how genomic sequence elements are read by trans-factors to control transcriptional burst sizes and frequencies. Moreover, I will introduce our recent Smart-seq3 method that provides unique abilities to count RNAs at both allele and isoform resolution.

This talk is part of the Genetics Seminar series.

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