ArticleProceedings of the National Academy of Sciences of the United States of America2016
Origin and evolution of developmental enhancers in the mammalian neocortex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.Genome medicine · 2021Pooled it
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- Evidence for compensatory evolution within pleiotropic regulatory elements.Genome research · 2024Article
- Resolving the three-dimensional interactome of Human Accelerated Regions during human and chimpanzee neurodevelopment.bioRxiv : the preprint server for biology · 2024Article
- CpG island turnover events predict evolutionary changes in enhancer activity.Genome biology · 2024Article
- Regulatory activity is the default DNA state in eukaryotes.Nature structural & molecular biology · 2024Article
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- Allele biased transcription factor binding across human brain regions gives mechanistic insight into eQTLs.bioRxiv : the preprint server for biology · 2023Article
- Multitissue H3K27ac profiling of GTEx samples links epigenomic variation to disease.Nature genetics · 2023Article
- Phylogenetic modeling of enhancer shifts in African mole-rats reveals regulatory changes associated with tissue-specific traits.Genome research · 2023Article
- Three-dimensional genome structure and function.MedComm · 2023Review
- Shifting landscapes: the role of 3D genomic organizations in gene regulatory strategies.Current opinion in genetics & development · 2023Review
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- De novo human brain enhancers created by single-nucleotide mutations.Science advances · 2023Article
- Enhancer architecture and chromatin accessibility constrain phenotypic space during Drosophila development.Developmental cell · 2023Article
- Introns: the "dark matter" of the eukaryotic genome.Frontiers in genetics · 2023Review
- Leveraging primate-specific genomic information for genetic studies of complex diseases.Frontiers in bioinformatics · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Morphological innovations such as the mammalian neocortex may involve the evolution of novel regulatory sequences. However, de novo birth of regulatory elements active during morphogenesis has not been extensively studied in mammals. Here, we use H3K27ac-defined regulatory elements active during human and mouse corticogenesis to identify enhancers that were likely active in the ancient mammalian forebrain. We infer the phylogenetic origins of these enhancers and find that ∼20% arose in the mammalian stem lineage, coincident with the emergence of the neocortex. Implementing a permutation strategy that controls for the nonrandom variation in the ages of background genomic sequences, we find that mammal-specific enhancers are overrepresented near genes involved in cell migration, cell signaling, and axon guidance. Mammal-specific enhancers are also overrepresented in modules of coexpressed genes in the cortex that are associated with these pathways, notably ephrin and semaphorin signaling. Our results also provide insight into the mechanisms of regulatory innovation in mammals. We find that most neocortical enhancers did not originate by en bloc exaptation of transposons. Young neocortical enhancers exhibit smaller H3K27ac footprints and weaker evolutionary constraint in eutherian mammals than older neocortical enhancers. Based on these observations, we present a model of the enhancer life cycle in which neocortical enhancers initially emerge from genomic background as short, weakly constrained "proto-enhancers." Many proto-enhancers are likely lost, but some may serve as nucleation points for complex enhancers to evolve.
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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.