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  • 1
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    Scanning human gene deserts for long-range enhancers (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nobrega, Marcelo A -- Ovcharenko, Ivan -- Afzal, Veena -- Rubin, Edward M -- HL66728/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 17;302(5644):413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14563999" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anura/genetics ; Base Sequence ; Conserved Sequence ; *DNA, Intergenic ; *Drosophila Proteins ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Gene Expression Regulation ; Genes, Reporter ; Humans ; Introns ; Mice ; Mice, Transgenic ; Nuclear Proteins/*genetics ; Synteny ; Takifugu/genetics ; Tetraodontiformes/genetics ; Xenopus/genetics ; Zebrafish/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-02-23
    Description: Sequence polymorphisms in a 58-kilobase (kb) interval on chromosome 9p21 confer a markedly increased risk of coronary artery disease (CAD), the leading cause of death worldwide. The variants have a substantial effect on the epidemiology of CAD and other life-threatening vascular conditions because nearly one-quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein-coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70-kb non-coding interval on mouse chromosome 4 affects cardiac expression of neighbouring genes, as well as proliferation properties of vascular cells. Chr4(Delta70kb/Delta70kb) mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the non-coding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4(Delta70kb/Delta70kb) mice, indicating that distant-acting gene regulatory functions are located in the non-coding CAD risk interval. Allele-specific expression of Cdkn2b transcripts in heterozygous mice showed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4(Delta70kb/Delta70kb) aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval has a pivotal role in regulation of cardiac Cdkn2a/b expression, and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938076/" 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/PMC2938076/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Visel, Axel -- Zhu, Yiwen -- May, Dalit -- Afzal, Veena -- Gong, Elaine -- Attanasio, Catia -- Blow, Matthew J -- Cohen, Jonathan C -- Rubin, Edward M -- Pennacchio, Len A -- DK59630/DK/NIDDK NIH HHS/ -- R01 HG003988/HG/NHGRI NIH HHS/ -- R01 HG003988-04/HG/NHGRI NIH HHS/ -- R01 HL082896/HL/NHLBI NIH HHS/ -- R01 HL082896-03/HL/NHLBI NIH HHS/ -- R21 HL098940/HL/NHLBI NIH HHS/ -- R21 HL098940-01/HL/NHLBI NIH HHS/ -- U01 HL066681/HL/NHLBI NIH HHS/ -- U01 HL066681-08/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Mar 18;464(7287):409-12. doi: 10.1038/nature08801. Epub 2010 Feb 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20173736" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta/pathology ; Cell Aging/genetics ; Cell Proliferation ; Cells, Cultured ; *Chromosome Deletion ; Chromosomes, Human, Pair 9/genetics ; Chromosomes, Mammalian/*genetics ; Coronary Artery Disease/*genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p15/deficiency/genetics ; Cyclin-Dependent Kinase Inhibitor p16/deficiency/genetics ; Embryo, Mammalian/embryology ; Gene Expression Regulation/genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Mice ; Myocytes, Smooth Muscle/pathology ; Survival Analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    ChIP-seq accurately predicts tissue-specific activity of enhancers (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-02-13
    Description: A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745234/" 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/PMC2745234/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Visel, Axel -- Blow, Matthew J -- Li, Zirong -- Zhang, Tao -- Akiyama, Jennifer A -- Holt, Amy -- Plajzer-Frick, Ingrid -- Shoukry, Malak -- Wright, Crystal -- Chen, Feng -- Afzal, Veena -- Ren, Bing -- Rubin, Edward M -- Pennacchio, Len A -- R01 HG003988/HG/NHGRI NIH HHS/ -- R01 HG003988-02/HG/NHGRI NIH HHS/ -- R01 NS062859/NS/NINDS NIH HHS/ -- R01 NS062859-01/NS/NINDS NIH HHS/ -- England -- Nature. 2009 Feb 12;457(7231):854-8. doi: 10.1038/nature07730.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212405" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromatin Immunoprecipitation/*methods ; Chromosome Mapping/*methods ; Conserved Sequence ; Embryo, Mammalian/embryology ; Extremities/*embryology ; *Gene Expression Regulation, Developmental ; Mesencephalon/*embryology ; Mice ; Prosencephalon/*embryology ; p300-CBP Transcription Factors/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Human-specific gain of function in a developmental enhancer (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-09-06
    Description: Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658639/" 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/PMC2658639/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prabhakar, Shyam -- Visel, Axel -- Akiyama, Jennifer A -- Shoukry, Malak -- Lewis, Keith D -- Holt, Amy -- Plajzer-Frick, Ingrid -- Morrison, Harris -- Fitzpatrick, David R -- Afzal, Veena -- Pennacchio, Len A -- Rubin, Edward M -- Noonan, James P -- 1-F32-GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367-02/GM/NIGMS NIH HHS/ -- HG003988/HG/NHGRI NIH HHS/ -- HL066681/HL/NHLBI NIH HHS/ -- MC_U127561093/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1346-50. doi: 10.1126/science.1159974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772437" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Body Patterning/*genetics ; Conserved Sequence ; Embryonic Development ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Extremities/*embryology ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Humans ; Limb Buds/embryology/metabolism ; Macaca mulatta/genetics ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; PAX9 Transcription Factor/metabolism ; Pan troglodytes/genetics ; Selection, Genetic ; Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Fine tuning of craniofacial morphology by distant-acting enhancers (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-10-26
    Description: The shape of the human face and skull is largely genetically determined. However, the genomic basis of craniofacial morphology is incompletely understood and hypothesized to involve protein-coding genes, as well as gene regulatory sequences. We used a combination of epigenomic profiling, in vivo characterization of candidate enhancer sequences in transgenic mice, and targeted deletion experiments to examine the role of distant-acting enhancers in craniofacial development. We identified complex regulatory landscapes consisting of enhancers that drive spatially complex developmental expression patterns. Analysis of mouse lines in which individual craniofacial enhancers had been deleted revealed significant alterations of craniofacial shape, demonstrating the functional importance of enhancers in defining face and skull morphology. These results demonstrate that enhancers are involved in craniofacial development and suggest that enhancer sequence variation contributes to the diversity of human facial morphology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991470/" 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/PMC3991470/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Attanasio, Catia -- Nord, Alex S -- Zhu, Yiwen -- Blow, Matthew J -- Li, Zirong -- Liberton, Denise K -- Morrison, Harris -- Plajzer-Frick, Ingrid -- Holt, Amy -- Hosseini, Roya -- Phouanenavong, Sengthavy -- Akiyama, Jennifer A -- Shoukry, Malak -- Afzal, Veena -- Rubin, Edward M -- FitzPatrick, David R -- Ren, Bing -- Hallgrimsson, Benedikt -- Pennacchio, Len A -- Visel, Axel -- 1R01DE01963/DE/NIDCR NIH HHS/ -- 1R01DE021708/DE/NIDCR NIH HHS/ -- 1U01DE020054/DE/NIDCR NIH HHS/ -- F32 GM105202/GM/NIGMS NIH HHS/ -- MC_PC_U127561093/Medical Research Council/United Kingdom -- MC_U127561093/Medical Research Council/United Kingdom -- R01 DE019638/DE/NIDCR NIH HHS/ -- R01 DE021708/DE/NIDCR NIH HHS/ -- R01 HG003988/HG/NHGRI NIH HHS/ -- R01 HG003991/HG/NHGRI NIH HHS/ -- R01HG003988/HG/NHGRI NIH HHS/ -- R01HG003991/HG/NHGRI NIH HHS/ -- U01 DE020054/DE/NIDCR NIH HHS/ -- U01 DE020060/DE/NIDCR NIH HHS/ -- U01DE020060/DE/NIDCR NIH HHS/ -- U54 HG006997/HG/NHGRI NIH HHS/ -- U54HG006997/HG/NHGRI NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Oct 25;342(6157):1241006. doi: 10.1126/science.1241006.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24159046" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Craniofacial Abnormalities/genetics/pathology ; Enhancer Elements, Genetic/genetics/*physiology ; Epigenesis, Genetic ; Face/abnormalities/*anatomy & histology ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Gene Targeting ; Maxillofacial Development/*genetics ; Mice ; Mice, Transgenic ; Sequence Deletion ; Skull/abnormalities/anatomy & histology/*growth & development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
    Electronic Resource
    Electronic Resource
    Depletion of cellular polyamines by α-difluoromethylornithine increases 1,3-bis(20chloroethyl)-1-nitrosourea-induced sister-chromatid exchanges
    Amsterdam : Elsevier
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 289 (1993), S. 107-114 
    Details
    ISSN: 0027-5107
    Keywords: 1,3-Bis(2-chloroethyl)-1-nitrosourea ; BCNU ; DFMO ; Polyamines ; Sister-chromatid exchanges ; α-Difluoromethylornithine
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0027-5107(93)90136-4
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  • 7
    Electronic Resource
    Electronic Resource
    Cultured human lymphocytes proliferate faster in medium lacking fetal calf serum and antibiotics
    Amsterdam : Elsevier
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 129 (1984), S. 207-213 
    Details
    ISSN: 0027-5107
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0027-5107(84)90153-2
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  • 8
    Electronic Resource
    Electronic Resource
    Adaptive response of human lymphocytes for the repair of radon-induced chromosomal damage
    Amsterdam : Elsevier
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 250 (1991), S. 299-306 
    Details
    ISSN: 0027-5107
    Keywords: Adaptive response ; Alpha particles ; Chromatid deletions ; Cytogenetic damage ; Radon
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0027-5107(91)90185-Q
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  • 9
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    Segregation of DNA polynucleotide strands into sister chromatids and the use of endoreduplicated cells to track sister chromatid exchanges induced by crosslinks, alkylations, or x-ray damage. (1996)
    National Academy of Sciences
    Details
    Publication Date: 1996-06-11
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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