VanBUG April 6th 6PM: Dr. Robin Dowell: Enhancer RNA Profiling Predicts Transcription Factor Activity
4 views
Skip to first unread message
Vanessa Guerra
Apr 1, 2017, 1:35:46 PM4/1/17
to sfu-omics
Post from the VanBUG team:
Title: Enhancer RNA Profiling Predicts Transcription Factor Activity
Abstract:
Transcription factors (TFs) exert their regulatory influence through the binding of enhancers, resulting in coordination of gene expression programs. Active enhancers are often characterized by the presence of short, unstable transcripts termed enhancer RNAs (eRNAs). While their function remains unclear, we demonstrate that eRNAs are a powerful readout of TF activity. We infer sites of eRNA origination across hundreds of publicly available nascent transcription datasets and show that eRNAs initiate from sites of TF binding. By quantifying the co-localization of TF-binding motifs and eRNA origins, we derive a simple statistic capable of inferring TF activity. In doing so, we uncover dozens of previously unexplored links between diverse stimuli and the TFs they affect. Our approach constitutes a fundamentally unique strategy for discovering links between TF activity and phenotypes.
Bio:
Robin Dowell is an Assistant Professor in the BioFrontiers Institute and Molecular, Cellular, and Developmental Biology at the University of Colorado in Boulder. Using a combination of machine learning and genome biology techniques, the Dowell laboratory seeks a mechanistic understanding of transcription regulation. To this end, the Dowell lab leverages a variety of experimental and computational approaches. Our recent focus has been on enhancers and their transcripts (eRNAs) which we detect and study by leveraging true measures of nascent transcription such as global run-on sequencing (GRO-seq). They have utilized the GRO-seq protocol to gain insight in the behavior of the tumor suppressor transcription factor p53 (Allen et. al. 2014) and CDK8-Mediator (Galbraith et. al. 2013). More recently they have significantly improved the GRO-seq protocol (Allen et. al. in prep.) and developed numerous improved algorithms for GRO-seq analysis (Azofeifa et. al. 2014; Azofeifa et. al. 2016; Lladser et. al. 2017; Azofeifa et. al. in review). Their work shows that eRNAs originate from active transcription factor binding sites. Furthermore, they leverage the pattern of eRNA usage to infer which transcription factors are currently active in any particular cell type. Finally, they have demonstrated the ability to identify the key initial transcriptional responders upon drug treatment.
VanBUG is generously sponsored by the UBC/SFU Bioinformatics Training Program, ECOSCOPE Training Program, MITACS, GenomeBC, and the Canadian Bioinformatics Workshops. We thank our major sponsors UBC/SFU Bioinformatics Training Program and welcome a new major sponsor, the ECOSCOPE NSERC CREATE Training Program.
___
Dear VanBUGger,
Please join us this coming Thursday, April 6th at 6PM with Dr. Robin Dowell from University of Colorado in Boulder. We are back at our usual location (BCCRC Auditorium) for the remaining sessions of this season.
Please join us this coming Thursday, April 6th at 6PM with Dr. Robin Dowell from University of Colorado in Boulder. We are back at our usual location (BCCRC Auditorium) for the remaining sessions of this season.
Title: Enhancer RNA Profiling Predicts Transcription Factor Activity
Abstract:
Transcription factors (TFs) exert their regulatory influence through the binding of enhancers, resulting in coordination of gene expression programs. Active enhancers are often characterized by the presence of short, unstable transcripts termed enhancer RNAs (eRNAs). While their function remains unclear, we demonstrate that eRNAs are a powerful readout of TF activity. We infer sites of eRNA origination across hundreds of publicly available nascent transcription datasets and show that eRNAs initiate from sites of TF binding. By quantifying the co-localization of TF-binding motifs and eRNA origins, we derive a simple statistic capable of inferring TF activity. In doing so, we uncover dozens of previously unexplored links between diverse stimuli and the TFs they affect. Our approach constitutes a fundamentally unique strategy for discovering links between TF activity and phenotypes.
Bio:
Robin Dowell is an Assistant Professor in the BioFrontiers Institute and Molecular, Cellular, and Developmental Biology at the University of Colorado in Boulder. Using a combination of machine learning and genome biology techniques, the Dowell laboratory seeks a mechanistic understanding of transcription regulation. To this end, the Dowell lab leverages a variety of experimental and computational approaches. Our recent focus has been on enhancers and their transcripts (eRNAs) which we detect and study by leveraging true measures of nascent transcription such as global run-on sequencing (GRO-seq). They have utilized the GRO-seq protocol to gain insight in the behavior of the tumor suppressor transcription factor p53 (Allen et. al. 2014) and CDK8-Mediator (Galbraith et. al. 2013). More recently they have significantly improved the GRO-seq protocol (Allen et. al. in prep.) and developed numerous improved algorithms for GRO-seq analysis (Azofeifa et. al. 2014; Azofeifa et. al. 2016; Lladser et. al. 2017; Azofeifa et. al. in review). Their work shows that eRNAs originate from active transcription factor binding sites. Furthermore, they leverage the pattern of eRNA usage to infer which transcription factors are currently active in any particular cell type. Finally, they have demonstrated the ability to identify the key initial transcriptional responders upon drug treatment.
Our Introductory Speaker is Yen-Yi Lin (PhD student in Dr. Cenk Sahinalp’s lab at SFU).
This year, we continue to invite trainee (students, PDFs, and RAs) to meet our featured speaker at 5PM in the BCCRC lunch room area to talk about science and career.
This year, you can continue to tune in to view the VanBUG talks live online! The permanent webcast link is http://vidyoreplay.computecanada.ca/replay/webcastShow.html?key=TAKdbjoDvIqKdLn. This technology is brought to you by Compute Canada and WestGrid with support from PHSA Telehelath.
Simply point your browser at the link during the live session to view the talk live. The webcast sessions are not interactive so if you have questions for the speakers please tweet your questions @VanBUG_ and we will try to respond to your questions live. Note that there is likely a 10-15 second delay with the video.
Sessions will also be recorded and archived with the presenters' consent and the links will be posted on the VanBUG website.
Note that pizza, beverage and lively social interactions are not available via Webcast! So there are still good reasons to attend VanBUGs in person.
Location:
675 West 10th Avenue
Gordon and Leslie Diamond Family Theatre
BC Cancer Agency
Date/Time:
675 West 10th Avenue
Gordon and Leslie Diamond Family Theatre
BC Cancer Agency
Date/Time:
April 6 2017
Start Time: 6:00 PM (Trainee Meet the Speakers sessions start at 5PM before the talk)
End Time: 7:30 PM (followed by pizza and drinks)
Start Time: 6:00 PM (Trainee Meet the Speakers sessions start at 5PM before the talk)
End Time: 7:30 PM (followed by pizza and drinks)
Rodrigo Goya
William Hsiao
Amy Lee
Kieran O'Neill
Raunak Shrestha
Thea Van Rossum
Phillip Richmond
Sam Hinshaw
Evan Morien
VanBUG is generously sponsored by the UBC/SFU Bioinformatics Training Program, ECOSCOPE Training Program, MITACS, GenomeBC, and the Canadian Bioinformatics Workshops. We thank our major sponsors UBC/SFU Bioinformatics Training Program and welcome a new major sponsor, the ECOSCOPE NSERC CREATE Training Program.
If you wish to subscribe and unsubscribe from our mailing list, please visit http://www.vanbug.org/mailing-list/ and follow the instructions there.
Reply all
Reply to author
Forward
0 new messages