Evolution of regulatory signatures in primate cortical neurons at cell-type resolution
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Abstract
Significance: The cerebral cortex of the human brain is a highly complex, heterogeneous tissue that contains many cell types that are exquisitely regulated at the level of gene expression by noncoding regulatory elements, presumably in a cell-type–dependent manner. However, assessing the regulatory elements in individual cell types is technically challenging, and therefore most of the previous studies on gene regulation were performed with bulk brain tissue. Here we analyze two major types of neurons isolated from the cerebral cortex of humans, chimpanzees, and rhesus macaques, and report complex patterns of cell-type–specific evolution of the regulatory elements in numerous genes. Many genes with evolving regulation are implicated in language abilities as well as psychiatric disorders.
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The number of enhancers that interact with promoters is strikingly correlated with gene regulation, as gene expression linearly increases with the number of physically interacting enhancers up to a total of 10 or more.
“Notably, the number of enhancers that interact with promoters was strikingly correlated with gene regulation, as gene expression linearly increased with the number of physically interacting enhancers up to a total of 10 or more (Supplementary Fig. 7e)3,28.”
From Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders (2021) · cites this paper as [28]
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Comparative transcriptomics reveals human-specific cortical features
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Self-citation
- Authors
- Kozlenkov, A., Vermunt, M. W., Apontes, P., Li, J., Hao, K., Sherwood, C. C., Hof, P. R., Ely, J. J., Wegner, M., Mukamel, E. A., Creyghton, M. P., Koonin, E. V., & Dracheva, S.
- Affiliations
- James J. Peters VA Medical Center (US)
- University Medical Center Utrecht (NL)
- University of California San Diego (US)
- Icahn School of Medicine at Mount Sinai (US)
- George Washington University (US)
- Holloman Air Force Base (US)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Erasmus MC (NL)
- National Institutes of Health (US)
- Corresponding author
- Creyghton, Menno P.
- Koonin, Eugene V.
- Dracheva, Stella
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-10-27
- Volume
- 117
- Issue
- 45
- Pages
- 28422-28432
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7668098
- OpenAlex
- W3095071594
- Cited by
- 30
- References
- 78
- Citations by year
- 2025: 5 · 2024: 9 · 2023: 11 · 2022: 4 · 2021: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- HHS | National Institutes of Health (MH103877, MH122590)
- Veteran Administration (BX001829)
- Veteran Adminsitration (BX002876)
- US Department of Health and Human Services (Intramural funds)
- Dutch Royal Academy of Sciences (Intramural funds)
- Parkinson's foundation (Stichting ParkinsonFonds)
- James S. McDonnell Foundation (220020293)
- National Science Foundation (INSPIRE SMA-1542848)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- human brain evolution, cortical neurons, glutamatergic projection neurons, GABAergic interneurons, H3K27ac, enhancer evolution, chimpanzees, rhesus monkeys, autism spectrum disorder, language, drug addiction, epigenomics, transcriptomics
- MeSH terms
- Autism Spectrum Disorder, Animals, Brain, Cerebral Cortex, Pan troglodytes, Humans, Interneurons, Macaca mulatta, Neurons, Primates, Regulatory Sequences, Nucleic Acid, Gene Expression, Evolution, Molecular, Histone Code, Epigenesis, Genetic, Regulatory Elements, Transcriptional, Epigenomics, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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