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A growing body of evidence supports the notion that variation in gene regulation plays a crucial role in both speciation and adaptation. However, a comprehensive functional understanding of the mechanisms underlying regulatory evolution remains elusive. In primates, one of the crucial missing pieces of information towards a better understanding of regulatory evolution is a comparative annotation of interactions between distal regulatory elements and promoters. Chromatin conformation capture technologies have enabled genome-wide quantifications of such distal 3D interactions. However, relatively little comparative research in primates has been done using such technologies. To address this gap, we used Hi-C to characterize 3D chromatin interactions in induced pluripotent stem cells (iPSCs) from humans and chimpanzees. We also used RNA-seq to collect gene expression data from the same lines. We generally observed that lower-order, pairwise 3D genomic interactions are conserved in humans and chimpanzees, but higher order genomic structures, such as topologically associating domains (TADs), are not as conserved. Inter-species differences in 3D genomic interactions are often associated with gene expression differences between the species. To provide additional functional context to our observations, we considered previously published chromatin data from human stem cells. We found that inter-species differences in 3D genomic interactions, which are also associated with gene expression differences between the species, are enriched for both active and repressive marks. Overall, our data demonstrate that, as expected, an understanding of 3D genome reorganization is key to explaining regulatory evolution.
Pubmed ID: 31323043
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A tool for mapping and performing quality control on Hi-C data.
View all literature mentionsEncyclopedia of DNA elements consisting of list of functional elements in human genome, including elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Enables scientific and medical communities to interpret role of human genome in biology and disease. Provides identification of common cell types to facilitate integrative analysis and new experimental technologies based on high-throughput sequencing. Genome Browser containing ENCODE and Epigenomics Roadmap data. Data are available for entire human genome.
View all literature mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsThe National Science Foundation's Graduate Research Fellowship Program (GRFP) helps ensure the vitality of the human resource base of science and engineering in the United States and reinforces its diversity. The program recognizes and supports outstanding graduate students in NSF-supported science, technology, engineering, and mathematics disciplines who are pursuing research-based master's and doctoral degrees in the U.S. and abroad. The NSF welcomes applications from all qualified students and strongly encourages under-represented populations, including women, under-represented racial and ethnic minorities, and persons with disabilities, to apply for this fellowship. Fellows share in the prestige and opportunities that become available when they are selected. Fellows benefit from a three-year annual stipend of $30,000 along with a $10,500 cost of education allowance for tuition and fees, a one-time $1,000 international travel allowance and the freedom to conduct their own research at any accredited U.S., or foreign institution of graduate education they choose. NSF Fellows are anticipated to become knowledge experts who can contribute significantly to research, teaching, and innovations in science and engineering. So that the nation can build fully upon the strength and creativity of a diverse society, the Foundation welcomes applications from all qualified individuals. Women, under-represented minorites and people with disabilities are encouraged to apply. Those with disabilities are additionally accommodated by the Foundation to provide for the most successful graduate experience possible. Sponsors: This program is supported by the National Science Foundation (NSF).
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