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  • 1
    Publication Date: 2010-03-20
    Description: Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor (TF) binding in several humans and a single chimpanzee by using chromatin immunoprecipitation followed by sequencing. The binding sites of RNA polymerase II (PolII) and a key regulator of immune responses, nuclear factor kappaB (p65), were mapped in 10 lymphoblastoid cell lines, and 25 and 7.5% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with single-nucleotide polymorphisms and genomic structural variants, and these differences were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing PolII binding between humans and chimpanzee suggests extensive divergence in TF binding. Our results indicate that many differences in individuals and species occur at the level of TF binding, and they provide insight into the genetic events responsible for these differences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938768/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938768/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasowski, Maya -- Grubert, Fabian -- Heffelfinger, Christopher -- Hariharan, Manoj -- Asabere, Akwasi -- Waszak, Sebastian M -- Habegger, Lukas -- Rozowsky, Joel -- Shi, Minyi -- Urban, Alexander E -- Hong, Mi-Young -- Karczewski, Konrad J -- Huber, Wolfgang -- Weissman, Sherman M -- Gerstein, Mark B -- Korbel, Jan O -- Snyder, Michael -- R01 CA077808/CA/NCI NIH HHS/ -- R01 CA077808-09/CA/NCI NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32 GM007205-34/GM/NIGMS NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U54 HG004558/HG/NHGRI NIH HHS/ -- U54 HG004558-04/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Apr 9;328(5975):232-5. doi: 10.1126/science.1183621. Epub 2010 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20299548" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; Chromatin Immunoprecipitation ; DNA Copy Number Variations ; DNA, Intergenic ; Female ; *Gene Expression Regulation ; Humans ; Male ; Pan troglodytes/genetics ; *Polymorphism, Single Nucleotide ; Protein Binding ; RNA Polymerase II/genetics/*metabolism ; Sequence Analysis, DNA ; Species Specificity ; Transcription Factor RelA/genetics/*metabolism ; Transcription Initiation Site
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-07-22
    Description: Developmental enhancers initiate transcription and are fundamental to our understanding of developmental networks, evolution and disease. Despite their importance, the properties governing enhancer-promoter interactions and their dynamics during embryogenesis remain unclear. At the beta-globin locus, enhancer-promoter interactions appear dynamic and cell-type specific, whereas at the HoxD locus they are stable and ubiquitous, being present in tissues where the target genes are not expressed. The extent to which preformed enhancer-promoter conformations exist at other, more typical, loci and how transcription is eventually triggered is unclear. Here we generated a high-resolution map of enhancer three-dimensional contacts during Drosophila embryogenesis, covering two developmental stages and tissue contexts, at unprecedented resolution. Although local regulatory interactions are common, long-range interactions are highly prevalent within the compact Drosophila genome. Each enhancer contacts multiple enhancers, and promoters with similar expression, suggesting a role in their co-regulation. Notably, most interactions appear unchanged between tissue context and across development, arising before gene activation, and are frequently associated with paused RNA polymerase. Our results indicate that the general topology governing enhancer contacts is conserved from flies to humans and suggest that transcription initiates from preformed enhancer-promoter loops through release of paused polymerase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghavi-Helm, Yad -- Klein, Felix A -- Pakozdi, Tibor -- Ciglar, Lucia -- Noordermeer, Daan -- Huber, Wolfgang -- Furlong, Eileen E M -- England -- Nature. 2014 Aug 7;512(7512):96-100. doi: 10.1038/nature13417. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Genome Biology Unit, D-69117 Heidelberg, Germany. ; 1] European Molecular Biology Laboratory, Genome Biology Unit, D-69117 Heidelberg, Germany [2]. ; Swiss Federal Institute of Technology, School of Life Sciences, CH-1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043061" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Chromosomes, Insect/genetics/metabolism ; DNA-Directed RNA Polymerases/*metabolism ; Drosophila melanogaster/embryology/*enzymology/*genetics ; Embryonic Development/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/genetics ; Genetic Loci/genetics ; Genome, Insect/genetics ; Humans ; Promoter Regions, Genetic/*genetics ; Transcription Initiation, Genetic ; Transcriptional Activation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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