An endogenous retrovirus regulates tumor-specific expression of the immune transcriptional regulator SP140.

Speckled Protein 140 (SP140) is a chromatin reader with critical roles regulating immune cell transcriptional programs, and SP140 splice variants are associated with immune diseases including Crohn's disease, multiple sclerosis, and chronic lymphocytic leukemia. SP140 expression is currently thought to be restricted to immune cells. However, by analyzing human transcriptomic datasets from a wide range of normal and cancer cell types, we found recurrent cancer-specific expression of SP140, driven by an alternative intronic promoter derived from an intronic endogenous retrovirus (ERV).

iSeq 2.0: A Modular and Interchangeable Toolkit for Interaction Screening in Yeast.

We developed a flexible toolkit for combinatorial screening in Saccharomyces cerevisiae, which generates large libraries of cells, each uniquely barcoded to mark a combination of DNA elements. This interaction sequencing platform (iSeq 2.0) includes genomic landing pads that assemble combinations through sequential integration of plasmids or yeast mating, 15 barcoded plasmid libraries containing split selectable markers (URA3, KanMX, HphMX, and NatMX), and an array of ∼24,000 "double-barcoder" strains that can make existing yeast libraries iSeq compatible.