STRUCTURAL ANNOTATION OF THE HUMAN GENOME
Job Dekker
Univ Of Massachusetts Med Sch Worcester, Worcester, Ma 01655
Grant 3R01HG003143-06S2 from National Human Genome Research Institute
Keywords: Affect; Allergy; Assay; Au element; B-globin; Bioassay; Biologic Assays; Biological; Biological Assay; C element; Carbon; Cell Line; Cell Lines, Strains; CellLine; Chromatin Loop; Chromatin Loop Domains; Chromosomes; DNA Loop; Data; Data Set; Dataset; Defect; Detection; Development; Disease; Disorder; Distal; Distant; Elements; Enhancers; Event; FISH Technic; FISH Technique; FISH analysis; Fluorescent in Situ Hybridization; Gene Action Regulation; Gene Arrangement; Gene Expression; Gene Expression Regulation; Gene Order; Gene Position; Gene Regulation; Gene Regulation Process; Gene Targeting; Genes; Genome; Genomics; Gold; Group Identifications; Human; Human Genome; Human, General; Hypersensitivity; In Situ Hybridization, Fluorescence; Investigators; Jobs; Man (Taxonomy); Man, Modern; Maps; Method LOINC Axis 6; Methodology; Methods; Molecular Configuration; Molecular Conformation; Molecular Stereochemistry; National Human Genome Research Institute; Occupations; Phase; Position; Positioning Attribute; Prevalence; Process; Professional Postions; Programs (PT); Programs [Publication Type]; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Regulation; Regulatory Element; RegulatoryElement; Relative; Relative (related person); Reporter; Research Personnel; Researchers; Role; Stretching; Targetings, Gene; Testing; Time; Transfection; base; beta Globin; combinatorial; conformation; conformational state; cultured cell line; disease/disorder; functional genomics; genetic element; histone modification; insight; novel; programs; social role; technology development; tool
Project start date: 2003-09-30
Project end date: 2011-03-31
Budget start date: 1-APR-2010
Budget end date: 31-MAR-2011
3R01HG003143-06S2 (2010): $555000
Sponsored Links Excellgen http://Excellgen.com
STRUCTURAL ANNOTATION OF THE HUMAN GENOME
Job Dekker, Associate Professor
Univ Of Massachusetts Med Sch Worcester, Worcester, Ma 01655
Grant 3R01HG003143-06S1 from National Human Genome Research Institute
Abstract: Regulation of gene expression is crucial for normal development and defects in this process can result in disease. A better understanding of the genetic elements that contribute to regulation of disease genes can reveal causes of disease and may spur development of novel treatments. Large-scale analyses of genomes, such as those initiated by the ENCODE project, have started to reveal the positions of many regulatory elements. However, in most cases it is not known which elements regulate any given gene. Understanding the relationships between regulatory elements and genes is complicated by the fact that the linear order of elements and genes along chromosomes often does not reflect functional relationships between them. For instance, regulatory elements may affect distal genes but not those located immediately next to them. Therefore, functional connections between genes and regulatory elements must be experimentally determined. This proposal is based on the hypothesis that regulatory elements physically associate with their target gene through formation of chromatin loops. We propose to test this hypothesis by mapping of looping interactions between genes and regulatory elements throughout the well-studied 1 % of the genome selected by the ENCODE consortium. We will detect chromatin loops using a unique approach, Chromosome Conformation Capture (3C) methodology. During the last 2 years we have developed a new high-throughput 3C application, called 5C (for 3C-carbon-copy) which employs microarrays or quantitative sequencing for detection of chromatin loops. We will further optimize 5C by analysis of the beta-globin locus (aim 1). We will employ 5C to identify chromatin loops between genes and regulatory elements throughout the well-studied ENCODE regions of the human genome (aim 2). For each gene we will identify distant elements such as enhancers that interact with its promoter. We will validate looping interactions by FISH (aim 3). We will test the function of looping elements using transient transfections and by integrating looping data with other data obtained by the ENCODE consortium such as histone modifications, DNasel hypersensitivity and target gene expression (aim 3). We will make looping data available through the UCSC genome browser. These studies will map the network of connections between genes and regulatory elements and will reveal new insights into the mechanisms that underlie long-range gene regulation
Keywords: Affect; Allergy; Assay; Au element; B-globin; Bioassay; Biologic Assays; Biological; Biological Assay; C element; Carbon; Cell Line; Cell Lines, Strains; CellLine; Chromatin Loop; Chromatin Loop Domains; Chromosomes; DNA Loop; Data; Data Set; Dataset; Defect; Detection; Development; Disease; Disorder; Distal; Distant; Elements; Enhancers; Event; FISH Technic; FISH Technique; FISH analysis; Fluorescent in Situ Hybridization; Gene Action Regulation; Gene Arrangement; Gene Expression; Gene Expression Regulation; Gene Order; Gene Position; Gene Regulation; Gene Regulation Process; Gene Targeting; Genes; Genome; Genome, Human; Genomics; Gold; Group Identifications; Human; Human Genome; Human, General; Hypersensitivity; Identifications, Group; In Situ Hybridization, Fluorescence; Investigators; Jobs; Man (Taxonomy); Man, Modern; Maps; Method LOINC Axis 6; Methodology; Methods; Molecular Configuration; Molecular Conformation; Molecular Stereochemistry; National Human Genome Research Institute; Occupations; Phase; Position; Positioning Attribute; Prevalence; Process; Professional Postions; Programs (PT); Programs [Publication Type]; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Regulation; Regulatory Element; RegulatoryElement; Relative; Relative (related person); Reporter; Research Personnel; Researchers; Role; Stretching; Targetings, Gene; Testing; Time; Transfection; base; beta Globin; combinatorial; conformation; conformational state; cultured cell line; disease/disorder; functional genomics; genetic element; histone modification; insight; novel; programs; social role; technology development; tool
Project start date: 2009-09-11
Project end date: 2011-08-31
Budget start date: 11-SEP-2009
Budget end date: 31-AUG-2011
3R01HG003143-06S1 (2009): $512696
Grants awarded to Job Dekker
Structural Annotation Of The Human Genome
Job Dekker
Univ Of Massachusetts Med Sch Worcester Worcester, Ma 01655
Grant 2R01HG003143-04 from National Human Genome Research Institute IRG: GCAT
Abstract: Regulation of gene expression is crucial for normal development and defects in this process can result in disease. A better understanding of the genetic elements that contribute to regulation of disease genes can reveal causes of disease and may spur development of novel treatments. Large-scale analyses of genomes, such as those initiated by the ENCODE project, have started to reveal the positions of many regulatory elements. However, in most cases it is not known which elements regulate any given gene. Understanding the relationships between regulatory elements and genes is complicated by the fact that the linear order of elements and genes along chromosomes often does not reflect functional relationships between them. For instance, regulatory elements may affect distal genes but not those located immediately next to them. Therefore, functional connections between genes and regulatory elements must be experimentally determined. This proposal is based on the hypothesis that regulatory elements physically associate with their target gene through formation of chromatin loops. We propose to test this hypothesis by mapping of looping interactions between genes and regulatory elements throughout the well-studied 1 % of the genome selected by the ENCODE consortium. We will detect chromatin loops using a unique approach, Chromosome Conformation Capture (3C) methodology. During the last 2 years we have developed a new high-throughput 3C application, called 5C (for 3C-carbon-copy) which employs microarrays or quantitative sequencing for detection of chromatin loops. We will further optimize 5C by analysis of the beta-globin locus (aim 1). We will employ 5C to identify chromatin loops between genes and regulatory elements throughout the well-studied ENCODE regions of the human genome (aim 2). For each gene we will identify distant elements such as enhancers that interact with its promoter. We will validate looping interactions by FISH (aim 3). We will test the function of looping elements using transient transfections and by integrating looping data with other data obtained by the ENCODE consortium such as histone modifications, DNasel hypersensitivity and target gene expression (aim 3). We will make looping data available through the UCSC genome browser. These studies will map the network of connections between genes and regulatory elements and will reveal new insights into the mechanisms that underlie long-range gene regulation.
Project start date: 2003-09-30
Project end date: 2010-03-31
2R01HG003143-04 (2007): $582000
5R01HG003143-03 (2005): $397500
5R01HG003143-02 (2004): $385700
1R01HG003143-01 (2003): $366820