Cell Type–Specific Chromatin Structure Determines the Targeting of V(D)J Recombinase Activity In Vitro
نویسندگان
چکیده
A common V(D)J recombinase that recognizes a conserved recombination signal sequence (RSS) mediates the assembly of immunoglobulin (Ig) and T cell receptor (TCR) genes in B and T cell precursors. The rearrangement of particular Ig and TCR gene segments, however, is tightly regulated with respect to cell lineage and developmental stage. Using an in vitro system, we analyzed recombinase cleavage of RSSs flanking Ig and TCR gene segments in nuclei. We found that both the lineage-specificity and temporal ordering of gene rearrangement is reflected in the accessibility of RSSs within chromatin to in vitro cleavage.
منابع مشابه
Histone Acetylation Determines the Developmentally Regulated Accessibility for T Cell Receptor γ Gene Recombination
Variable/diversity/joining (V[D]J) recombination of the T cell receptor (TCR) and immunoglobulin (Ig) genes is regulated by chromatin accessibility of the target locus to the recombinase in a lineage- and stage-specific manner. Histone acetylation has recently been proposed as a molecular mechanism underlying the accessibility control. Here, we investigate the role for histone acetylation in th...
متن کاملChanges in Locus-specific V(D)J Recombinase Activity Induced by Immunoglobulin Gene Products during B Cell Development
The process of V(D)J recombination is crucial for regulating the development of B cells and for determining their eventual antigen specificity. Here we assess the developmental regulation of the V(D)J recombinase directly, by monitoring the double-stranded DNA breaks produced in the process of V(D)J recombination. This analysis provides a measure of recombinase activity at immunoglobulin heavy ...
متن کاملNucleosome structure completely inhibits in vitro cleavage by the V(D)J recombinase.
Lineage specificity and temporal ordering of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement are reflected in the accessibility of recombination signal sequences (RSSs) within chromatin to in vitro cleavage by the V(D)J recombinase. In this report, we investigated the basis of this regulation by testing the ability of purified RAG1 and RAG2 proteins to initiate cleavage on posi...
متن کاملV(D)j Recombination Becomes Accessible
The diverse antigen receptor repertoires of B and T lym-phocytes are generated by somatic rearrangement of Ig and TCR V, D, and J gene segments during lymphocyte development. A basic mechanistic understanding of V(D)J re-combination reaction is now at hand. The process is initiated by recombinase proteins recombination activating gene (RAG)-1 and RAG-2, which bind to recombination signal sequen...
متن کاملVariegated Transcriptional Activation of the Immunoglobulin κ Locus in Pre-B Cells Contributes to the Allelic Exclusion of Light-Chain Expression
ated at the level of regulated gene rearrangement—an individual B cell makes only one productive (in-frame) gene rearrangement at each locus, the second allele being excluded from expression. One of the outstanding questions in immunology is how productive V(D)J re-Several types of evidence support the hypothesis that V(D)J recombinase activity is regulated by the accessibility of rearranging l...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cell
دوره 85 شماره
صفحات -
تاریخ انتشار 1996