Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation Article Swipe
Zeqian Gao
,
Alastair Smith
,
James N. Scott
,
Sarah L. Bevington
,
Joan Boyes
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkad741
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkad741
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 antisense 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.
Related Topics
Concepts
Enhancer
Biology
Enhancer RNAs
Transcription (linguistics)
Transcription factor
Promoter
Sense (electronics)
Locus (genetics)
Antisense RNA
Gene
Regulation of gene expression
Molecular biology
Cell biology
Genetics
RNA
Gene expression
Chemistry
Physical chemistry
Philosophy
Linguistics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/nar/gkad741
- https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad741/51538858/gkad741.pdf
- OA Status
- gold
- Cited By
- 2
- References
- 89
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386704832
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4386704832Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/nar/gkad741Digital Object Identifier
- Title
-
Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-09-13Full publication date if available
- Authors
-
Zeqian Gao, Alastair Smith, James N. Scott, Sarah L. Bevington, Joan BoyesList of authors in order
- Landing page
-
https://doi.org/10.1093/nar/gkad741Publisher landing page
- PDF URL
-
https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad741/51538858/gkad741.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad741/51538858/gkad741.pdfDirect OA link when available
- Concepts
-
Enhancer, Biology, Enhancer RNAs, Transcription (linguistics), Transcription factor, Promoter, Sense (electronics), Locus (genetics), Antisense RNA, Gene, Regulation of gene expression, Molecular biology, Cell biology, Genetics, RNA, Gene expression, Chemistry, Physical chemistry, Philosophy, LinguisticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
-
2023: 2Per-year citation counts (last 5 years)
- References (count)
-
89Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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