How chromatin remodelling allows shuffling of immunoglobulin heavy chain genes
Cellular identity is determined by the switching on and off of lineage-specific genes. This dynamic process is regulated by a highly co-ordinated series of chromatin remodelling mechanisms that control DNA accessibility to facilitate transcription, replication and recombination. The identity of an i...
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Published in | Molecular bioSystems Vol. 4; no. 8; pp. 790 - 798 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
England
01.01.2008
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Abstract | Cellular identity is determined by the switching on and off of lineage-specific genes. This dynamic process is regulated by a highly co-ordinated series of chromatin remodelling mechanisms that control DNA accessibility to facilitate transcription, replication and recombination. The identity of an individual B-lymphocyte is defined by the expression of a unique antibody protein, composed of two identical immunoglobulin heavy and two identical light chain polypeptides, which recognize a single foreign antigen with high specificity. However, the mammalian adaptive immune system requires an enormous variety of antibody-expressing B cells to combat the millions of foreign antigens it may encounter. This diversity is generated primarily at the multigene immunoglobulin loci by V(D)J recombination, a specialised form of DNA recombination in which numerous variable (V), diversity (D) and joining (J) genes are cut and pasted together in a strict order to allow shuffling of immunoglobulin genes. The mouse immunoglobulin heavy chain (Igh) locus is the largest known multigene locus. It spans approximately 3 Mb and comprises more than 200 genes. Its size and complexity pose an enormous logistic challenge to the chromatin remodelling machinery, but recent major advances in our understanding of how the 200 genes are shuffled have begun to reveal an exquisitely co-ordinated set of chromatin remodelling mechanisms which exploit every aspect of nuclear dynamics, and provide a global view of multigene regulation. This review will explore the numerous processes implicated in opening up and positioning of the locus to enable shuffling of the Igh locus genes, including non-coding RNA transcription, histone modifications, transcription factors, nuclear relocation and locus contraction. |
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AbstractList | Cellular identity is determined by the switching on and off of lineage-specific genes. This dynamic process is regulated by a highly co-ordinated series of chromatin remodelling mechanisms that control DNA accessibility to facilitate transcription, replication and recombination. The identity of an individual B-lymphocyte is defined by the expression of a unique antibody protein, composed of two identical immunoglobulin heavy and two identical light chain polypeptides, which recognize a single foreign antigen with high specificity. However, the mammalian adaptive immune system requires an enormous variety of antibody-expressing B cells to combat the millions of foreign antigens it may encounter. This diversity is generated primarily at the multigene immunoglobulin loci by V(D)J recombination, a specialised form of DNA recombination in which numerous variable (V), diversity (D) and joining (J) genes are cut and pasted together in a strict order to allow shuffling of immunoglobulin genes. The mouse immunoglobulin heavy chain (Igh) locus is the largest known multigene locus. It spans approximately 3 Mb and comprises more than 200 genes. Its size and complexity pose an enormous logistic challenge to the chromatin remodelling machinery, but recent major advances in our understanding of how the 200 genes are shuffled have begun to reveal an exquisitely co-ordinated set of chromatin remodelling mechanisms which exploit every aspect of nuclear dynamics, and provide a global view of multigene regulation. This review will explore the numerous processes implicated in opening up and positioning of the locus to enable shuffling of the Igh locus genes, including non-coding RNA transcription, histone modifications, transcription factors, nuclear relocation and locus contraction. |
Author | Bowen, Adam J Corcoran, Anne E |
Author_xml | – sequence: 1 givenname: Adam J surname: Bowen fullname: Bowen, Adam J organization: Laboratory of Chromatin and Gene Expression, Babraham Institute, Babraham Research Campus, Cambridge, UK – sequence: 2 givenname: Anne E surname: Corcoran fullname: Corcoran, Anne E |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18633479$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1002_bies_200900067 crossref_primary_10_3390_cancers13235949 crossref_primary_10_1016_j_molcel_2009_05_011 crossref_primary_10_1007_s12185_014_1637_4 |
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SubjectTerms | Animals Cell Nucleus - metabolism Chromatin - metabolism Chromatin Assembly and Disassembly Gene Rearrangement, B-Lymphocyte, Heavy Chain Genes, Immunoglobulin Histones - metabolism Humans Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Heavy Chains - metabolism Immunoglobulin Variable Region - genetics Immunoglobulin Variable Region - immunology Immunoglobulin Variable Region - metabolism Nucleosomes - metabolism Recombination, Genetic Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic |
Title | How chromatin remodelling allows shuffling of immunoglobulin heavy chain genes |
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