The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA181397 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR618726.fastq.gz | Fastqsanger.gz | |||
| SRR618727_1.fastq.gz | Fastqsanger.gz | |||
| SRR618727_2.fastq.gz | Fastqsanger.gz | |||
| SRR618728.fastq.gz | Fastqsanger.gz | |||
| SRR618729_1.fastq.gz | Fastqsanger.gz |
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Project description:The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution. ChIP-Seq and RNA-Seq of autopod tissue of developing limb buds of Human (E33-E47), rhesus (E31-E36), and mouse (E10.5-E13.5). No raw data are provided for human samples. Human alignments were anonymized by removing sequence information and converting to bed format.
2013-07-02 | E-GEOD-42413 | biostudies-arrayexpress
Project description:The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution.
2013-07-02 | GSE42413 | GEO
Project description:The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution.
| S-EPMC3785101 | biostudies-literature
Project description:<p>We used epigenetic profiling to map active enhancers in the developing human limb and cortex as described in two published studies: <ul> <li>Cotney J, Leng J, Yin J, Reilly SK et al. The evolution of lineage-specific regulatory activities in the human embryonic limb. <a href="https://www.ncbi.nlm.nih.gov/pubmed/23827682">Cell 2013</a>;154(1):185-96. </li> <li>Reilly SK, Yin J, Ayoub AE, Emera D et al. Evolutionary changes in promoter and enhancer activity during human corticogenesis. <a href="https://www.ncbi.nlm.nih.gov/pubmed/25745175">Science 2015</a>;347(6226):1155-9.</li> </ul> </p> <p> We also used ChIP-seq to map binding sites for the chromatin modifier <a href="https://www.ncbi.nlm.nih.gov/gene/?term=CHD8"><i>CHD8</i></a> in the developing human brain, as described in one published study: <ul> <li>Cotney J, Muhle RA, Sanders SJ, Liu L et al. The autism-associated chromatin modifier <a href="https://www.ncbi.nlm.nih.gov/gene/?term=CHD8"><i>CHD8</i></a> regulates other autism risk genes during human neurodevelopment. <a href="https://www.ncbi.nlm.nih.gov/pubmed/25752243">Nat Commun 2015</a>;6:6404.</li> </ul> </p> <p> We are also depositing primary human sequence reads related to processed datasets in the Gene Expression Omnibus under the following accession numbers: <a href="https://www.ncbi.nlm.nih.gov/gds/?term=GSE42413">GSE42413</a> (Cotney et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/23827682">2013</a>); <a href="https://www.ncbi.nlm.nih.gov/gds/?term=GSE63649">GSE63649</a> (Reilly et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/25745175">2015</a>); <a href="https://www.ncbi.nlm.nih.gov/gds/?term=GSE57369">GSE57369</a> (Cotney et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/25752243">2015</a>). </p>
| phs001226 | dbGaP
Project description:H3K4me1 methyltransferases MLL3 (KMT2C) and MLL4 (KMT2D) are critical for enhancer activation, cell differentiation and development. However, roles of MLL3/4 enzymatic activities and MLL3/4-mediated enhancer H3K4me1 in these processes remain unclear. Here, we report that constitutive elimination of both MLL3 and MLL4 enzymatic activities prevents initiation of gastrulation and leads to early embryonic lethality in mice. However, selective elimination of MLL3/4 enzymatic activities in embryonic, but not extraembryonic, lineages leaves gastrulation largely intact. Consistently, embryonic stem cells (ESCs) lacking MLL3/4 enzymatic activities can differentiate towards the three embryonic germ layers but show aberrant differentiation to extraembryonic endoderm and trophectoderm. The failure in extraembryonic endoderm differentiation can be attributed to markedly reduced enhancer-binding of the lineage-determining transcription factor GATA6. Furthermore, we show that MLL3/4-catalyzed H3K4me1 is largely dispensable for enhancer activation during ESC differentiation. Together, our findings suggest a lineage-selective, but enhancer activation-independent, role of MLL3/4 methyltransferase activities in early embryonic development and ESC differentiation.
2023-01-25 | GSE154475 | GEO
Project description:Genome-wide comparative analyses of the open chromatin profiles between equivalent stages of mouse and pig limb bud development reveal the extensive functional divergence of their limb regulomes. These alterations affect evolutionary conserved regions located in the genomic landscapes of genes with essential functions during limb development. This analysis uncovers the widespread regulatory changes that appear to underlie the morphological diversion of the artiodactyl limb from the pentadactyl blueprint of tetrapods.
2020-03-31 | GSE126291 | GEO
Project description:Genome-wide comparative analyses of the open chromatin profiles between equivalent stages of mouse and pig limb bud development reveal the extensive functional divergence of their limb regulomes. These alterations affect evolutionary conserved regions located in the genomic landscapes of genes with essential functions during limb development. This analysis uncovers the widespread regulatory changes that appear to underlie the morphological diversion of the artiodactyl limb from the pentadactyl blueprint of tetrapods.
2020-03-31 | GSE126292 | GEO
Project description:Regulatory divergence during limb evolution
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Project description:Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming
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Project description:Regulatory divergence during pig limb evolution
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