Dynamics and function of distal regulatory elements during neurogenesis and neuroplasticity Article Swipe
Sudhir Thakurela
,
Sanjeeb Kumar Sahu
,
Angela Garding
,
Vijay Tiwari
·
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1101/gr.190926.115
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1101/gr.190926.115
Gene regulation in mammals involves a complex interplay between promoters and distal regulatory elements that function in concert to drive precise spatiotemporal gene expression programs. However, the dynamics of the distal gene regulatory landscape and its function in the transcriptional reprogramming that underlies neurogenesis and neuronal activity remain largely unknown. Here, we performed a combinatorial analysis of genome-wide data sets for chromatin accessibility (FAIRE-seq) and the enhancer mark H3K27ac, revealing the highly dynamic nature of distal gene regulation during neurogenesis, which gets progressively restricted to distinct genomic regions as neurons acquire a post-mitotic, terminally differentiated state. We further find that the distal accessible and active regions serve as target sites for distinct transcription factors that function in a stage-specific manner to contribute to the transcriptional program underlying neuronal commitment and maturation. Mature neurons respond to a sustained activity of NMDA receptors by epigenetic reprogramming at a large number of distal regulatory regions as well as dramatic reorganization of super-enhancers. Such massive remodeling of the distal regulatory landscape in turn results in a transcriptome that confers a transient loss of neuronal identity and gain of cellular plasticity. Furthermore, NMDA receptor activity also induces many novel prosurvival genes that function in neuroprotective pathways. Taken together, these findings reveal the dynamics of the distal regulatory landscape during neurogenesis and uncover novel regulatory elements that function in concert with epigenetic mechanisms and transcription factors to generate the transcriptome underlying neuronal development and activity.
Related Topics
Concepts
Biology
Neurogenesis
Enhancer
Reprogramming
Epigenetics
Transcription factor
Regulation of gene expression
Transcriptome
Gene regulatory network
Neuroscience
Chromatin
Gene
Cell biology
Genetics
Gene expression
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1101/gr.190926.115
- http://genome.cshlp.org/content/25/9/1309.full.pdf
- OA Status
- hybrid
- Cited By
- 46
- References
- 81
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2159717426
All OpenAlex metadata
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- OpenAlex ID
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https://openalex.org/W2159717426Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/gr.190926.115Digital Object Identifier
- Title
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Dynamics and function of distal regulatory elements during neurogenesis and neuroplasticityWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2015Year of publication
- Publication date
-
2015-07-13Full publication date if available
- Authors
-
Sudhir Thakurela, Sanjeeb Kumar Sahu, Angela Garding, Vijay TiwariList of authors in order
- Landing page
-
https://doi.org/10.1101/gr.190926.115Publisher landing page
- PDF URL
-
https://genome.cshlp.org/content/25/9/1309.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
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https://genome.cshlp.org/content/25/9/1309.full.pdfDirect OA link when available
- Concepts
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Biology, Neurogenesis, Enhancer, Reprogramming, Epigenetics, Transcription factor, Regulation of gene expression, Transcriptome, Gene regulatory network, Neuroscience, Chromatin, Gene, Cell biology, Genetics, Gene expressionTop concepts (fields/topics) attached by OpenAlex
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46Total citation count in OpenAlex
- Citations by year (recent)
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2025: 4, 2024: 2, 2023: 2, 2022: 3, 2021: 1Per-year citation counts (last 5 years)
- References (count)
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81Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| institutions_distinct_count | 4 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/17 |
| sustainable_development_goals[0].score | 0.4699999988079071 |
| sustainable_development_goals[0].display_name | Partnerships for the goals |
| citation_normalized_percentile.value | 0.93782165 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |