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| Status |
Public on Aug 28, 2023 |
| Title |
Temporal Analyses Reveal a Pivotal Role for Sense and Anti-sense Enhancer RNAs in Coordinate Immunoglobulin Lambda Locus Activation |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Transcription enhancers are essential activators of V(D)J recombination that orchestrate non-coding transcription through complementary, unrearranged gene segments. How transcription is coordinately increased at spatially distinct promoters, however, remains poorly understood. Using the murine immunoglobulin lambda (Igλ) locus as model, we find that three enhancer-like elements in the 3’ Igλ domain, Eλ3-1, HSCλ1 and HSE-1, show strikingly similar transcription factor binding dynamics and close spatial proximity, suggesting that they form an active enhancer hub. Temporal analyses show coordinate recruitment of complementary V and J gene segments to this hub, with comparable transcription factor binding dynamics to that at enhancers. We find further that E2A, p300, Mediator and Integrator bind to enhancers as early events, whereas YY1 recruitment and eRNA synthesis occur later, corresponding to transcription activation. Remarkably, the interplay between sense and anti-sense enhancer RNA is central to both active enhancer hub formation and coordinate Igλ transcription: Antisense Eλ3-1 eRNA represses Igλ activation whereas temporal analyses demonstrate that accumulating levels of sense eRNA boost YY1 recruitment to stabilise enhancer hub/promoter interactions and lead to coordinate transcription activation. These studies therefore demonstrate for the first time a critical role for threshold levels of sense versus antisense eRNA in locus activation.
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| Overall design |
ATAC-seq performed on the PIPER-15 cell line
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| Contributor(s) |
Smith AL, Gao Z, Boyes J |
| Citation(s) |
37702072 |
| Submission date |
Aug 02, 2023 |
| Last update date |
Nov 13, 2023 |
| Contact name |
Alastair Smith |
| E-mail(s) |
alastair.smith@ndcls.ox.ac.uk
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| Organization name |
University of Oxford
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| Street address |
The MRC Weatherall Institute of Molecular Medicine
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| City |
Oxford |
| State/province |
England |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM7677576 |
ATAC-seq in DMSO-treated PIPER-15 cells replicate 1 |
| GSM7677577 |
ATAC-seq in DMSO-treated PIPER-15 cells replicate 2 |
| GSM7677578 |
ATAC-seq in 4-OH tamoxifen treated (12hrs) PIPER-15 cells replicate 1 |
| GSM7677579 |
ATAC-seq in 4-OH tamoxifen treated (12hrs) PIPER-15 cells replicate 2 |
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| Relations |
| BioProject |
PRJNA1001396 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE239925_RAW.tar |
372.5 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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