A dynamic RNA hub facilitates activation induced cytidine deaminase recruitment to the immunoglobulin heavy chain locus

Description

This data set contains raw data for our publication titled "A dynamic RNA hub facilitates activation induced cytidine deaminase recruitment to the immunoglobulin heavy chain locus". The data set included raw gel images and microscopy images for all experiments included in our study. Activation-induced cytidine deaminase (AID) converts cytosines to uracils within the actively transcribed switch regions to initiate DNA uracil repair and formation of DNA double strand breaks required for immunoglobulin class switch recombination (CSR). How AID specifically targets switch regions remains a key unanswered question. Using a multimodal live cell single molecule imaging approach, we demonstrate that intronic switch regions promote robust transcription by enhancing polymerase engagement and persistent transcriptional bursts, resulting in the formation of a dynamic RNA hub consisting of numerous nascent switch transcripts simultaneously tethered to the IgH locus. We further demonstrate that AID interacts with switch region RNA in vivo, and that this interaction is required for recruitment of AID to the IgH locus. Together, our findings show that the RNA hub formed by nascent switch region transcripts may be part of a “class switch recombination center” and drives the specific recruitment of AID to the IgH locus to initiate CSR.

Institutions

• Michigan State University

  Michigan, East Lansing

Categories

Funders

• National Institute of General Medical Sciences

  National Institutes of Health

  Bethesda

  Grant ID: DP2 GM142307
• National Institute of Allergy and Infectious Diseases

  National Institutes of Health

  Bethesda

  Grant ID: R01 AI139039

Licence