Repeat organization and epigenetic regulation of the DH-Cμ domain of the immunoglobulin heavy-chain gene locusi
Repeat organization and epigenetic regulation of the DH-Cμ domain of the immunoglobulin heavy-chain gene locusi
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DOI：
10.1016/j.molcel.2007.07.010
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发表时间：
2007-09-07
期刊：
影响因子：
16
通讯作者：
Sen, Ranjan
中科院分区：
文献类型：
--
作者：
Chakraborty, Tirtha;Chowdhury, Dipanjan;Sen, Ranjan
鼠免疫球蛋白重链（IgH）基因重组的第一步发生在含有多样性（D-H）和连接（J（H））基因区段但不含有可变（V-H）基因区段的染色体结构域内。在这里，我们表明，该域的染色质状态是显着的异质性。具体地说，只有5 '和3'端的D-H基因片段携带活性染色质修饰，而插入的D（H）与通过进行中的组蛋白脱乙酰化维持的异染色质标记相关。插入的D（H）形成串联重复序列的一部分，该串联重复序列表达组织特异性反义定向转录物。我们提出，插入DH基因被重复诱导的表观遗传沉默积极抑制，这反映在它们在DJ（H）连接处的代表性比侧翼D-H基因少。
The first steps of murine immunoglobulin heavy-chain (IgH) gene recombination take place within a chromosomal domain that contains diversity (D-H) and joining (J(H)) gene segments, but not variable (V-H) gene segments. Here we show that the chromatin state of this domain is markedly heterogeneous. Specifically, only 5'- and 3'-most D-H gene segments carry active chromatin modifications, whereas intervening D(H)s are associated with heterochromatic marks that are maintained by ongoing histone deacetylation. The intervening D(H)s form part of a tandemly repeated sequence that expresses tissue-specific, antisense oriented transcripts. We propose that the intervening DH genes are actively suppressed by repeat-induced epigenetic silencing, which is reflected in their infrequent representation in DJ(H) junctions compared to the flanking D-H genes.