Epigenetic regulation of human-specific gene expression in the prefrontal cortex
Abstract Background Changes in gene expression levels during brain development are thought to have played an important role in the evolution of human cognition. With the advent of high-throughput sequencing technologies, changes in brain developmental expression patterns, as well as human-specific b...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-023-01612-3 |
| _version_ | 1797817767855915008 |
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| author | Weifen Sun Gangcai Xie Xi Jiang Philipp Khaitovich Dingding Han Xiling Liu |
| author_facet | Weifen Sun Gangcai Xie Xi Jiang Philipp Khaitovich Dingding Han Xiling Liu |
| author_sort | Weifen Sun |
| collection | DOAJ |
| description | Abstract Background Changes in gene expression levels during brain development are thought to have played an important role in the evolution of human cognition. With the advent of high-throughput sequencing technologies, changes in brain developmental expression patterns, as well as human-specific brain gene expression, have been characterized. However, interpreting the origin of evolutionarily advanced cognition in human brains requires a deeper understanding of the regulation of gene expression, including the epigenomic context, along the primate genome. Here, we used chromatin immunoprecipitation sequencing (ChIP-seq) to measure the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac), both of which are associated with transcriptional activation in the prefrontal cortex of humans, chimpanzees, and rhesus macaques. Results We found a discrete functional association, in which H3K4me3HP gain was significantly associated with myelination assembly and signaling transmission, while H3K4me3HP loss played a vital role in synaptic activity. Moreover, H3K27acHP gain was enriched in interneuron and oligodendrocyte markers, and H3K27acHP loss was enriched in CA1 pyramidal neuron markers. Using strand-specific RNA sequencing (ssRNA-seq), we first demonstrated that approximately 7 and 2% of human-specific expressed genes were epigenetically marked by H3K4me3HP and H3K27acHP, respectively, providing robust support for causal involvement of histones in gene expression. We also revealed the co-activation role of epigenetic modification and transcription factors in human-specific transcriptome evolution. Mechanistically, histone-modifying enzymes at least partially contribute to an epigenetic disturbance among primates, especially for the H3K27ac epigenomic marker. In line with this, peaks enriched in the macaque lineage were found to be driven by upregulated acetyl enzymes. Conclusions Our results comprehensively elucidated a causal species-specific gene-histone-enzyme landscape in the prefrontal cortex and highlighted the regulatory interaction that drove transcriptional activation. |
| first_indexed | 2024-03-13T08:58:19Z |
| format | Article |
| id | doaj.art-4bafe8b6b5c4493ebb8b21449359ae5d |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-03-13T08:58:19Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-4bafe8b6b5c4493ebb8b21449359ae5d2023-05-28T11:27:34ZengBMCBMC Biology1741-70072023-05-0121112010.1186/s12915-023-01612-3Epigenetic regulation of human-specific gene expression in the prefrontal cortexWeifen Sun0Gangcai Xie1Xi Jiang2Philipp Khaitovich3Dingding Han4Xiling Liu5Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of JusticeCAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, CASCAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, CASCAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, CASCAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, CASShanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of JusticeAbstract Background Changes in gene expression levels during brain development are thought to have played an important role in the evolution of human cognition. With the advent of high-throughput sequencing technologies, changes in brain developmental expression patterns, as well as human-specific brain gene expression, have been characterized. However, interpreting the origin of evolutionarily advanced cognition in human brains requires a deeper understanding of the regulation of gene expression, including the epigenomic context, along the primate genome. Here, we used chromatin immunoprecipitation sequencing (ChIP-seq) to measure the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac), both of which are associated with transcriptional activation in the prefrontal cortex of humans, chimpanzees, and rhesus macaques. Results We found a discrete functional association, in which H3K4me3HP gain was significantly associated with myelination assembly and signaling transmission, while H3K4me3HP loss played a vital role in synaptic activity. Moreover, H3K27acHP gain was enriched in interneuron and oligodendrocyte markers, and H3K27acHP loss was enriched in CA1 pyramidal neuron markers. Using strand-specific RNA sequencing (ssRNA-seq), we first demonstrated that approximately 7 and 2% of human-specific expressed genes were epigenetically marked by H3K4me3HP and H3K27acHP, respectively, providing robust support for causal involvement of histones in gene expression. We also revealed the co-activation role of epigenetic modification and transcription factors in human-specific transcriptome evolution. Mechanistically, histone-modifying enzymes at least partially contribute to an epigenetic disturbance among primates, especially for the H3K27ac epigenomic marker. In line with this, peaks enriched in the macaque lineage were found to be driven by upregulated acetyl enzymes. Conclusions Our results comprehensively elucidated a causal species-specific gene-histone-enzyme landscape in the prefrontal cortex and highlighted the regulatory interaction that drove transcriptional activation.https://doi.org/10.1186/s12915-023-01612-3H3K4me3H3K27acChIP-seqStrand-specific RNA-seq (ssRNA-seq)Prefrontal cortex (PFC)Transcription factor (TF) |
| spellingShingle | Weifen Sun Gangcai Xie Xi Jiang Philipp Khaitovich Dingding Han Xiling Liu Epigenetic regulation of human-specific gene expression in the prefrontal cortex BMC Biology H3K4me3 H3K27ac ChIP-seq Strand-specific RNA-seq (ssRNA-seq) Prefrontal cortex (PFC) Transcription factor (TF) |
| title | Epigenetic regulation of human-specific gene expression in the prefrontal cortex |
| title_full | Epigenetic regulation of human-specific gene expression in the prefrontal cortex |
| title_fullStr | Epigenetic regulation of human-specific gene expression in the prefrontal cortex |
| title_full_unstemmed | Epigenetic regulation of human-specific gene expression in the prefrontal cortex |
| title_short | Epigenetic regulation of human-specific gene expression in the prefrontal cortex |
| title_sort | epigenetic regulation of human specific gene expression in the prefrontal cortex |
| topic | H3K4me3 H3K27ac ChIP-seq Strand-specific RNA-seq (ssRNA-seq) Prefrontal cortex (PFC) Transcription factor (TF) |
| url | https://doi.org/10.1186/s12915-023-01612-3 |
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