Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development.
Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development.
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DOI：
10.4049/jimmunol.182.1.44
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Feeney, Ann J.
中科院分区：
文献类型：
--
作者：
Degner, Stephanie C.;Wong, Timothy P.;Jankevicius, Gytis;Feeney, Ann J.
大的Igh和Igκ基因座的收缩使所有V基因（每个基因座的长度为2.5 Mb）接近DJH或Jκ基因。CTCF是一种通过长链染色体环调控基因表达的转录因子。因此，我们假设CTCF可能对Ig基因座的收缩至关重要，但没有在任何V基因座中描述CTCF位点。利用ChIP-Chip，我们在VH和Vκ区发现了许多CTCF位点。然而，CTCF在Igh位点的富集，而不是Igκ位点，在整个分化过程中基本不变，这表明CTCF单独结合不能负责阶段特异性环。由于内聚蛋白可以与CTCF共定位，我们对内聚蛋白亚基Rad21进行了ChIP检测，并在所有Ig位点发现了谱系和阶段特异性的Rad21向CTCF募集。黏结蛋白与CTCF位点的差异结合可能促进多个环的形成，从而有效地进行V(D)J重组。
Contraction of the large Igh and Igκ loci brings all V genes, spanning >2.5 Mb in each locus, in proximity to DJH or Jκ genes. CTCF is a transcription factor that regulates gene expression by long-range chromosomal looping. We therefore hypothesized CTCF may be crucial for the contraction of the Ig loci, but no CTCF sites have been described in any V loci. Utilizing ChIP-Chip, we demonstrated many CTCF sites in the VH and Vκ regions. However, CTCF enrichment in the Igh locus, but not the Igκ locus, was largely unchanged throughout differentiation, suggesting that CTCF binding alone cannot be responsible for stage-specific looping. Since cohesin can colocalize with CTCF, we performed ChIP for the cohesin subunit Rad21, and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites at may promote multiple loop formation and thus effective V(D)J recombination.
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