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Evolutionary changes in promoter and enhancer activity during corticogenesis (non-human)

ABSTRACT: Evolutionary changes in promoter and enhancer activity during corticogenesis (non-human)

PROVIDER: PRJNA259649 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1560370.fastq.gz	Fastqsanger.gz
	SRR1560380.fastq.gz	Fastqsanger.gz
	SRR1560390.fastq.gz	Fastqsanger.gz
	SRR1560400.fastq.gz	Fastqsanger.gz
	SRR1560371.fastq.gz	Fastqsanger.gz

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Evolutionary changes in promoter and enhancer activity during corticogenesis (non-human)

Project description:Evolutionary changes in gene regulation during cortical development likely contributed to the expansion and specialization of the cortex. However, the lack of a regulatory map of the embryonic cortex has hindered identification of these changes and the biological processes they influenced. We performed genome-wide epigenetic profiling to compare promoter and enhancer activity during corticogenesis in rhesus and mouse. We identified 2,855 promoters and 8,996 enhancers that have gained activity in based on increased epigenetic marking. To detect biological pathways enriched for these changes, we mapped promoters and enhancers exhibiting epigenetic gains onto modules of co-expressed genes constructed using spatio-temporally rich expression data from developing cortex. We identified multiple modules enriched in lineage epigenetic gains. Gains in enriched modules were associated with genes functioning in neuronal proliferation and migration, cortical patterning, and the extracellular matrix. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes in corticogenesis, providing insight into cortical evolution.

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Evolutionary changes in promoter and enhancer activity during human corticogenesis (human)

Project description:Evolutionary changes in gene regulation during cortical development likely contributed to the expansion and specialization of the cortex in humans. However, the lack of a regulatory map of the human embryonic cortex has hindered identification of these changes and the biological processes they influenced. We performed genome-wide epigenetic profiling to compare promoter and enhancer activity during corticogenesis in human, rhesus, and mouse. We identified 2,855 promoters and 8,996 enhancers that have gained activity in human based on increased epigenetic marking. To detect biological pathways enriched for these changes, we mapped promoters and enhancers exhibiting epigenetic gains onto modules of co-expressed genes constructed using spatio-temporally rich expression data from developing human cortex. We identified multiple modules enriched in human lineage epigenetic gains. Gains in enriched modules were associated with genes functioning in neuronal proliferation and migration, cortical patterning, and the extracellular matrix. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes in corticogenesis, providing insight into human cortical evolution.

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Evolutionary genomics. Evolutionary changes in promoter and enhancer activity during human corticogenesis.

Project description:Human higher cognition is attributed to the evolutionary expansion and elaboration of the human cerebral cortex. However, the genetic mechanisms contributing to these developmental changes are poorly understood. We used comparative epigenetic profiling of human, rhesus macaque, and mouse corticogenesis to identify promoters and enhancers that have gained activity in humans. These gains are significantly enriched in modules of coexpressed genes in the cortex that function in neuronal proliferation, migration, and cortical-map organization. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting that they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes during corticogenesis, providing insight into human cortical evolution.

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Evolutionary changes in promoter and enhancer activity during human corticogenesis

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Enhancer Cis Elements Instruct Promoter-Enhancer Interaction, Promoter-Enhancer Insulation and Compartmental Segregation

Project description:Enhancers harbor instructions encoded for the interactions between cis-elements and transcription factors to orchestrate lineage specific gene programs. Here we developed a modified method for chromosome conformation capture (3C), named MID Hi-C, to reveal how in mouse embryonic stem cells differential cooperation of enhancers and the chromatin remodeler BAF, as instructed by the underlying transcription factor motifs, modulate enhancer-promoter communication. We show that BAF-dependent enhancers permit genomic interactions beyond enhancer boundaries. BAF-dependent enhancers do not dictate genomic interactions within enhancer-promoter loop domains but rather act to instruct remote enhancer-promoter communication. In contrast, BAF-independent enhancers interact with promoter regions within tightly insulated enhancer-promoter loop domains that are marked by promoter and enhancer boundary elements. In addition, enhancer activeness modulated by BAF enforces compartment segregation. Based on these observations, we propose that enhancer cis elements instruct with great precision BAF-induced enhancer-promoter communication and compartmental segregation.

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