Nuclear matrix interactions at the human protamine domain - A working model of potentiation
Nuclear matrix interactions at the human protamine domain - A working model of potentiation
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DOI：
10.1074/jbc.m409415200
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发表时间：
2004-12-10
影响因子：
4.8
通讯作者：
Krawetz, SA
中科院分区：
文献类型：
--
作者：
Martins, RP;Ostermeier, GC;Krawetz, SA
紧凑的真核生物基因组必须有选择地开放，以允许反式因子进入顺式调控元件，以克服基因转录的主要障碍。控制染色质结构域选择性开放(即增强)的机制仍然知之甚少。在缺乏明确的位点控制区的情况下，核基质被认为是调节多基因PRM1-->；PRM2-->；TNP2人鱼精蛋白结构域开放的主要候选者。为了直接检测其作用，创建了四个转基因小鼠系，它们具有围绕鱼精蛋白结构域的不同配置的核基质附着区(MARS)。我们发现，一旦火星被移走，轨道就会受到位置效应的影响。仅3‘MAR一项就足以防止沉默。总之，结合这个结构域的火星可能会协同调节这个基因簇的各个成员的表达。有趣的是，火星可能传递了一种选择性繁殖优势，因此同时带有5‘和3’火星的结构会以更高的频率传递给他们的后代。因此，与PRM1-->；PRM2-->；TNP2鱼精蛋白结构域结合的MARS具有多种不同的功能。
The compact eukaryotic genome must be selectively opened to grant trans-factor access to cis-regulatory elements to overcome the primary barrier to gene transcription. The mechanism that governs the selective opening of chromatin domains (i.e. potentiation) remains poorly understood. In the absence of a well defined locus control region, the nuclear matrix is considered the primary candidate regulating the opening of the multigenic PRM1 --> PRM2 --> TNP2 human protamine domain. To directly examine its role, four lines of transgenic mice with different configurations of flanking nuclear matrix attachment regions (MARs) encompassing the protamine domain were created. We show that upon removal of the MARs, the locus becomes subject to position effects. The 3' MAR alone may be sufficient to protect against silencing. In concert, the MARs bounding this domain likely synergize to regulate the expression of the various members of this gene cluster. Interestingly, the MARs may convey a selective reproductive advantage, such that constructs bearing both 5' and 3' MARs are passed to their offspring with greater frequency. Thus, the MARs bounding the PRM1 --> PRM2 --> TNP2 protamine domain have many and varied functions.