Elements between the IgH variable (V) and diversity (D) clusters influence antisense transcription and lineage-specific V(D)J recombination. 2010

Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
Department of Genetics, The Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Ig and T-cell receptor (TCR) variable-region gene exons are assembled from component variable (V), diversity (D) and joining (J) gene segments during early B and T cell development. The RAG1/2 endonuclease initiates V(D)J recombination by introducing DNA double-strand breaks at borders of the germ-line segments. In mice, the Ig heavy-chain (IgH) locus contains, from 5' to 3', several hundred V(H) gene segments, 13 D segments, and 4 J(H) segments within a several megabase region. In developing B cells, IgH variable-region exon assembly is ordered with D to J(H) rearrangement occurring on both alleles before appendage of a V(H) segment. Also, IgH V(H) to DJ(H) rearrangement does not occur in T cells, even though DJ(H) rearrangements occur at low levels. In these contexts, V(D)J recombination is controlled by modulating substrate gene segment accessibility to RAG1/2 activity. To elucidate control elements, we deleted the 100-kb intergenic region that separates the V(H) and D clusters (generating ΔV(H)-D alleles). In both B and T cells, ΔV(H)-D alleles initiated high-level antisense and, at lower levels, sense transcription from within the downstream D cluster, with antisense transcripts extending into proximal V(H) segments. In developing T lymphocytes, activated germ-line antisense transcription was accompanied by markedly increased IgH D-to-J(H) rearrangement and substantial V(H) to DJ(H) rearrangement of proximal IgH V(H) segments. Thus, the V(H)-D intergenic region, and likely elements within it, can influence silencing of sense and antisense germ-line transcription from the IgH D cluster and thereby influence targeting of V(D)J recombination.

UI MeSH Term Description Entries
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D008817 Mice, Mutant Strains Mice bearing mutant genes which are phenotypically expressed in the animals. Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D015326 Gene Rearrangement, B-Lymphocyte, Heavy Chain Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES. B-Cell Heavy Chain Gene Rearrangement,B-Lymphocyte Heavy Chain Gene Rearrangement,B-Lymphocyte Mu Chain Gene Rearrangement,B Cell Heavy Chain Gene Rearrangement,B Cell Mu Chain Gene Rearrangement,B Lymphocyte Heavy Chain Gene Rearrangement,B Lymphocyte Mu Chain Gene Rearrangement

Related Publications

Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
June 2004, Nature immunology,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
February 2011, Immunity,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
August 2007, Molecular and cellular biology,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
December 2014, Nature communications,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
June 2023, Proceedings of the National Academy of Sciences of the United States of America,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
February 2015, Proceedings of the National Academy of Sciences of the United States of America,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
February 2004, The Journal of experimental medicine,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
December 2004, Nature,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
December 1996, Immunology,
Cosmas C Giallourakis, and Andrew Franklin, and Chunguang Guo, and Hwei-Ling Cheng, and Hye Suk Yoon, and Michael Gallagher, and Thomas Perlot, and Milena Andzelm, and Andrew J Murphy, and Lynn E Macdonald, and George D Yancopoulos, and Frederick W Alt
April 2023, bioRxiv : the preprint server for biology,
Copied contents to your clipboard!