Antisense Intergenic transcription precedes Igh D-to-J recombination and is controlled by the intronic enhancer Eμ
Antisense Intergenic transcription precedes Igh D-to-J recombination and is controlled by the intronic enhancer Eμ
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DOI：
10.1128/mcb.02407-06
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发表时间：
2007-08-01
影响因子：
5.3
通讯作者：
Corcoran, Anne E.
中科院分区：
文献类型：
--
作者：
Bolland, Daniel J.;Wood, Andrew L.;Corcoran, Anne E.
V(D)J 重组被认为是通过重组酶机器染色质可及性的改变来调节的，但其机制仍不清楚。我们之前提出，在 pro-B 细胞中整个小鼠 Igh V-H 区域激活的反义基因间转录会重塑染色质，以实现 V-H 到 DJ(H) 重组。利用 RNA 荧光原位杂交，我们现在表明反义基因间转录在 D-to-J 重组之前发生在整个 Igh D(H)J(H) 区域，表明这是 V(D)J 重组中广泛存在的过程。转录在 Igh 内含子增强子 E-mu 附近开始，在缺乏该增强子的小鼠中被消除，表明 E-mu 调节 D-H 反义转录。最近证明 E-mu 可以调节 Igh 基因座的 D-H 到 J(H) 重组。总之，这些数据表明 E-mu 通过激活这种形式的种系 Igh 转录来控制 D-H 到 J(H) 重组，从而提供了一种长程、持续的机制，通过该机制 E-mu 可以调节整个 D-H 区域的染色质可及性。相比之下，E-mu 缺失对 V-H 反义基因间转录没有影响，而 V-H 反义基因间转录很少与 D-H 反义转录相关，这表明这些过程在 V(D)J 重组的连续阶段存在差异调节和独立作用。这些结果支持反义基因间转录在实现重组机制方面的指导作用。
V(D)J recombination is believed to be regulated by alterations in chromatin accessibility to the recombinase machinery, but the mechanisms responsible remain unclear. We previously proposed that antisense intergenic transcription, activated throughout the mouse Igh V-H region in pro-B cells, remodels chromatin for V-H-to-DJ(H) recombination. Using RNA fluorescence in situ hybridization, we now show that antisense intergenic transcription occurs throughout the Igh D(H)J(H) region before D-to-J recombination, indicating that this is a widespread process in V(D)J recombination. Transcription initiates near the Igh intronic enhancer E-mu and is abrogated in mice lacking this enhancer, indicating that E-mu regulates D-H antisense transcription. E-mu was recently demonstrated to regulate D-H-to-J(H) recombination of the Igh locus. Together, these data suggest that E-mu controls D-H-to-J(H) recombination by activating this form of germ line Igh transcription, thus providing a long-range, processive mechanism by which E-mu can regulate chromatin accessibility throughout the D-H region. In contrast, E-mu deletion has no effect on V-H antisense intergenic transcription, which is rarely associated with D-H antisense transcription, suggesting differential regulation and separate roles for these processes at sequential stages of V(D)J recombination. These results support a directive role for antisense intergenic transcription in enabling access to the recombination machinery.