ArticlePLoS biology2012
Human-specific histone methylation signatures at transcription start sites in prefrontal neurons.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
73 citing papers in PubMed, 127 citations in OpenAlex.
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- Integrative Proteome Analysis Revels 3-Hydroxybutyrate Exerts Neuroprotective Effect by Influencing Chromatin Bivalency.International journal of molecular sciences · 2023Article
- The evolutionary origin of psychosis.Frontiers in psychiatry · 2023Article
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- High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy.Acta neuropathologica communications · 2022Article
- Chromatin Profiling Techniques: Exploring the Chromatin Environment and Its Contributions to Complex Traits.International journal of molecular sciences · 2021Review
- Evolution of DNA methylation in the human brain.Nature communications · 2021Article
- TBC1D3 promotes neural progenitor proliferation by suppressing the histone methyltransferase G9a.Science advances · 2021Article
- Parsing the Functional Impact of Noncoding Genetic Variants in the Brain Epigenome.Biological psychiatry · 2021Review
- The methylation landscape and its role in domestication and gene regulation in the chicken.Nature ecology & evolution · 2020Article
- Differences between human and chimpanzee genomes and their implications in gene expression, protein functions and biochemical properties of the two species.BMC genomics · 2020Review
- Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons.Nature neuroscience · 2020Article
- Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia.Translational psychiatry · 2019Article
- Epigenetic-genetic chromatin footprinting identifies novel and subject-specific genes active in prefrontal cortex neurons.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Reorganization of 3D genome structure may contribute to gene regulatory evolution in primates.PLoS genetics · 2019Article
- Transgenic rhesus monkeys carrying the humanNational science review · 2019Article
- Risk gene-set and pathways in 22q11.2 deletion-related schizophrenia: a genealogical molecular approach.Translational psychiatry · 2019Article
13 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility genes. Regulatory sequences at DPP10 and additional loci carried a strong footprint of hominid adaptation, including elevated nucleotide substitution rates and regulatory motifs absent in other primates (including archaic hominins), with evidence for selective pressures during more recent evolution and adaptive fixations in modern populations. Chromosome conformation capture at two neurodevelopmental disease loci, 2q14.1 and 16p11.2, revealed higher order chromatin structures resulting in physical contact of multiple human-specific H3K4me3 peaks spaced 0.5-1 Mb apart, in conjunction with a novel cis-bound antisense RNA linked to Polycomb repressor proteins and downregulated DPP10 expression. Therefore, coordinated epigenetic regulation via newly derived TSS chromatin could play an important role in the emergence of human-specific gene expression networks in brain that contribute to cognitive functions and neurological disease susceptibility in modern day humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.