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Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [H3K27ac]

ABSTRACT: Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [H3K27ac]

PROVIDER: PRJNA1034579 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26628149.fastq.gz	Fastqsanger.gz
	SRR26628150.fastq.gz	Fastqsanger.gz
	SRR26628151_1.fastq.gz	Fastqsanger.gz
	SRR26628151_2.fastq.gz	Fastqsanger.gz
	SRR26628152.fastq.gz	Fastqsanger.gz

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Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex

Project description:Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex

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Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [marmoset]

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Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [H3K27ac]

Project description:Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of neocortex at the molecular and cellular level remains to be elucidated. We investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset, and mouse with single cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome and chromosomal conformation profiles from a total of over 180,000 cells. For each modality, we determined species-specific, divergent, and conserved gene expression and epigenetic features at multiple levels. We find that cell type-specific gene expression evolves more rapidly than broadly expressed genes, and that epigenetic status at distal candidate cis-regulatory elements (cCREs) evolves faster than promoters. Strikingly, transposable elements (TEs) contribute to nearly 80% of the human-specific cCREs in cortical cells. Through machine learning, we develop sequence-based predictors of cCREs in different species, and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Lastly, we show that epigenetic conservation combined with sequence similarity help uncover functional cis-regulatory elements and enhance our ability to interpret genetic variants contributing to neurological disease and traits.

2023-11-28 | GSE246760 | GEO

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex

2023-10-31 | GSE229169 | GEO

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [marmoset]

Project description:Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains to be elucidated. We investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset, and mouse with single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome, and chromosomal conformation profiles from a total of over 180,000 cells. For each modality, we determined species-specific, divergent, and conserved gene expression and epigenetic features at multiple levels. We find that cell type-specific gene expression evolves more rapidly than broadly expressed genes and that epigenetic status at distal candidate cis-regulatory elements (cCREs) evolves faster than promoters. Strikingly, transposable elements (TEs) contribute to nearly 80% of the human-specific cCREs in cortical cells. Through machine learning, we develop sequence-based predictors of cCREs in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Lastly, we show that epigenetic conservation combined with sequence similarity helps uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.

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Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [Macaque]

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The Regulatory Evolution of the Primate Fine-Motor System

Project description:In mammals, fine motor control is essential for skilled behavior, and is subserved by specialized subdivisions of the primary motor cortex (M1) and other components of the brain’s motor circuitry. We profiled the epigenomic state of several components of the Rhesus macaque motor system, including subdivisions of M1 corresponding to hand and orofacial control. We compared this to open chromatin data from M1 in rat, mouse, and human. We found broad similarities as well as unique specializations in open chromatin regions (OCRs) between M1 subdivisions and other brain regions, as well as species- and lineage-specific differences reflecting their evolutionary histories. By distinguishing shared mammalian M1 OCRs from primate- and human-specific specializations, we highlight gene regulatory programs that could subserve the evolution of skilled motor behaviors such as speech and tool use. Further, in order to predict candidate enhancers in additional species for which primary data was not available, we developed machine learning models trained on genome sequence across species.

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The Regulatory Evolution of the Primate Fine-Motor System

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Epigenomic annotation of gene regulatory alterations during evolution of the primate brain

Project description:While genome sequencing has identified numerous non-coding alterations between primate species, which of these are regulatory and potentially relevant to the evolution of the human brain is unclear. Here, we annotate cis-regulatory elements (CREs) in the human, rhesus macaque and chimpanzee genome using ChIP-sequencing in different anatomical parts of the adult brain. We find high similarity in the genomic positioning of CREs between rhesus macaque and humans, suggesting that the majority of these elements were already present in a common ancestor 25 million years ago. Most of the observed regulatory changes between humans and rhesus macaque occurred prior to the ancestral separation of humans and chimpanzee, leaving a modest set of regulatory elements with predicted human-specificity. Our data refine previous predictions and hypotheses on the consequences of genomic changes between primate species, and allow the identification of regulatory alterations relevant to the evolution of the brain. ChIP-Sequencing for H3K27ac on 8 distinct brain regions from human (three biological replicates per brain region), chimpanzee (two biological replicates per brain region) and rhesus macaque (three biological replicates per brain region).

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