Poster abstracts
Poster number 95 submitted by Simon Lizarazo
A Multi-tissue and cancer atlas of Pol III activity uncovers context-specific transcriptional expansion to genes implicated in disease progression
Simon Lizarazo (Molecular and Integrative Physiology, University of Illinois Urbana-Champaign), Sihang Zhou (Cell and Developmental Biology, University of Illinois Urbana-Champaign), Ruiying Cheng (Cell and Developmental Biology, University of Illinois Urbana-Champaign), Rajendra K C (Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign), Kevin Van Bortle (Cell and Developmental Biology, University of Illinois Urbana-Champaign)
Abstract:
RNA polymerase III (Pol III) produces a plethora of small noncoding RNA
involved in nearly all cellular processes, from transcription regulation and
splicing to RNA stability, translation, and protein turnover. Though Pol III
activity is broadly coupled with cellular demands for protein synthesis and
growth, a more precise understanding of gene-level dynamics and context-
specific expression patterns remain missing, in part due to multiple
challenges related to sequencing and mapping Pol III-derived small ncRNA
species. Here, we establish a multi-tissue map of Pol III activity across 19
tissues and 22 primary cancers by comprehensively profiling the chromatin
accessibility of Pol III-transcribed genes (e.g. tRNA, 5S rRNA, U6 snRNA,
7SL SRP RNA, etc.). Our framework relies on the unique relationship
between gene accessibility and Pol III transcription and defines a binary
gene “on” vs. “off” state across ~500 ATAC-seq datasets. Using an
information entropy method to characterize multi-context uniformity, we
provide a definition of the “core” Pol III transcriptome universally active in
all specialized tissues and catalog genes with varied levels of context
specificity. Notably, our genomic atlas points to variable levels of
restriction and expansion of Pol III activity across tissues, including sharp
contraction of the Pol III transcriptome in heart tissues and frequent
expansion across diverse cancers. We discover divergent epigenomic
regulatory features at universal and tissue-specific genes, including
evidence for multiple repressive mechanisms that likely contribute to the
silencing of context-specific Pol III-transcribed genes. These findings
provide a resource for better understanding Pol III dynamics in tissues and
the link between Pol III overactivity and small RNA biogenesis in cancer.
Keywords: RNA Polymerase III, Genomic Atlas