Department of Molecular Biology, Princeton University, Princeton, United States; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russian Federation
Xin Yang Bing
Lewis Sigler Institute, Princeton University, Princeton, United States
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russian Federation; Department of Biology and General Genetics, Sechenov University, Moscow, Russian Federation
Michael Levine
Lewis Sigler Institute, Princeton University, Princeton, United States
Pavel Georgiev
Department of the Control of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russian Federation
Though long non-coding RNAs (lncRNAs) represent a substantial fraction of the Pol II transcripts in multicellular animals, only a few have known functions. Here we report that the blocking activity of the Bithorax complex (BX-C) Fub-1 boundary is segmentally regulated by its own lncRNA. The Fub-1 boundary is located between the Ultrabithorax (Ubx) gene and the bxd/pbx regulatory domain, which is responsible for regulating Ubx expression in parasegment PS6/segment A1. Fub-1 consists of two hypersensitive sites, HS1 and HS2. HS1 is an insulator while HS2 functions primarily as an lncRNA promoter. To activate Ubx expression in PS6/A1, enhancers in the bxd/pbx domain must be able to bypass Fub-1 blocking activity. We show that the expression of the Fub-1 lncRNAs in PS6/A1 from the HS2 promoter inactivates Fub-1 insulating activity. Inactivation is due to read-through as the HS2 promoter must be directed toward HS1 to disrupt blocking.
