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Elements between the IgH variable (V) and diversity (D) clusters influence antisense transcription and lineage-specific V(D)J recombination.
Giallourakis, Cosmas C; Franklin, Andrew; Guo, Chunguang; Cheng, Hwei-Ling; Yoon, Hye Suk; Gallagher, Michael; Perlot, Thomas; Andzelm, Milena; Murphy, Andrew J; Macdonald, Lynn E; Yancopoulos, George D; Alt, Frederick W.
Afiliación
  • Giallourakis CC; Department of Genetics, The Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A ; 107(51): 22207-12, 2010 Dec 21.
Article en En | MEDLINE | ID: mdl-21123744
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.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transcripción Genética / Región Variable de Inmunoglobulina / Linfocitos B / Reordenamiento Génico de Cadena Pesada de Linfocito B / ARN sin Sentido / Cadenas Pesadas de Inmunoglobulina Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2010 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transcripción Genética / Región Variable de Inmunoglobulina / Linfocitos B / Reordenamiento Génico de Cadena Pesada de Linfocito B / ARN sin Sentido / Cadenas Pesadas de Inmunoglobulina Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2010 Tipo del documento: Article