Department of Genetics, Harvard Medical School, Harvard, Boston, USA
Stirling Churchman was a postdoc with Jonathan Weissmann, UCSF, where she pioneered native elongating transcript sequencing (NET-seq, Nature 2011). In 2011 she started her own lab at Harvard Medical School where they study the molecular mechanisms that control and coordinate transcription with co-transcriptional processes, including splicing, chromatin remodeling and termination. She will tell us about her recent work on human transcription profiling at single nucliotide resoultion (Cell, 2015).
Major features of transcription by human RNA Polymerase II (Pol II) remain poorly defined due to a lack of quantitative approaches for visualizing Pol II progress at nucleotide resolution. We developed a simple and powerful approach for performing native elongating transcript sequencing (NET-seq) in human cells that globally maps strand-specific Pol II density at nucleotide resolution. NET-seq exposes a mode of antisense transcription that originates downstream and converges on transcription from the canonical promoter. Convergent transcription is associated with a distinctive chromatin configuration and is characteristic of lower-expressed genes. Integration of NET-seq with genomic footprinting data reveals stereotypic Pol II pausing coincident with transcription factor occupancy. Finally, exons retained in mature transcripts display Pol II pausing signatures that differ markedly from skipped exons, indicating an intrinsic capacity for Pol II to recognize exons with different processing fates. Together, human NET-seq exposes the topography and regulatory complexity of human gene expression.
Host: Johan Elf
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