The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Topoisomerases facilitate transcription of long genes linked to autism
Open accessAbstract
Topoisomerases are expressed throughout the developing and adult brain and are mutated in some individuals with autism spectrum disorder (ASD). However, how topoisomerases are mechanistically connected to ASD is unknown. Here we find that topotecan, a topoisomerase 1 (TOP1) inhibitor, dose-dependently reduces the expression of extremely long genes in mouse and human neurons, including nearly all genes that are longer than 200 kilobases. Expression of long genes is also reduced after knockdown of Top1 or Top2b in neurons, highlighting that both enzymes are required for full expression of long genes. By mapping RNA polymerase II density genome-wide in neurons, we found that this length-dependent effect on gene expression was due to impaired transcription elongation. Interestingly, many high-confidence ASD candidate genes are exceptionally long and were reduced in expression after TOP1 inhibition. Our findings suggest that chemicals and genetic mutations that impair topoisomerases could commonly contribute to ASD and other neurodevelopmental disorders.
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Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
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De novo mutations revealed by whole-exome sequencing are strongly associated with autism
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c-Myc Regulates Transcriptional Pause Release
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From the genetic architecture to synaptic plasticity in autism spectrum disorder
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Activity-Regulated Transcription: Bridging the Gap between Neural Activity and Behavior
Yap, E.-L., & Greenberg, M. E. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.013 · Cited by 706
Disruption of DNA-methylation-dependent long gene repression in Rett syndrome
Gabel, H. W., Kinde, B., Stroud, H., Gilbert, C. S., Harmin, D. A., Kastan, N. R., Hemberg, M., Ebert, D. H., & Greenberg, M. E. (2015) · Nature · doi:10.1038/nature14319 · Cited by 569
The code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain
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Metadata
- Authors
- King, I. F., Yandava, C. N., Mabb, A. M., Hsiao, J. S., Huang, H.-S., Pearson, B. L., Calabrese, J. M., Starmer, J., Parker, J. S., Magnuson, T., Chamberlain, S. J., Philpot, B. D., & Zylka, M. J.
- Venue
- Nature
- Published
- 2013-08-28
- Volume
- 501
- Issue
- 7465
- Pages
- 58-62
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2056013470
- Cited by
- 438
- References
- 47
- FWCI
- 20.64
- Type
- journal article
- Language
- en
- Open access
- green
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- King, I. F., Yandava, C. N., Mabb, A. M., Hsiao, J. S., Huang, H.-S., Pearson, B. L., Calabrese, J. M., Starmer, J., Parker, J. S., Magnuson, T., Chamberlain, S. J., Philpot, B. D., & Zylka, M. J. (2013). Topoisomerases facilitate transcription of long genes linked to autism. Nature. https://doi.org/10.1038/nature12504
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