lncRNA read-through regulates the BX-C insulator Fub-1

Author:

Ibragimov Airat12ORCID,Bing Xin Yang3,Shidlovskii Yulii V45ORCID,Levine Michael3,Georgiev Pavel6,Schedl Paul1ORCID

Affiliation:

1. Department of Molecular Biology, Princeton University

2. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences

3. Lewis Sigler Institute, Princeton University

4. Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology Russian Academy of Sciences

5. Department of Biology and General Genetics, Sechenov University

6. Department of the Control of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences

Abstract

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.

Funder

National Institute of General Medical Sciences

Russian Science Foundation

Ministry of Science and Higher Education of the Russian Federation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference59 articles.

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