The LRS and SIN domains: Two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencing
The LRS and SIN domains: Two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencing
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DOI：
10.1128/mcb.00248-06
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发表时间：
2006-12-01
影响因子：
5.3
通讯作者：
Peterson, Craig L.
中科院分区：
文献类型：
--
作者：
Fry, Christopher J.;Norris, Anne;Peterson, Craig L.
遗传实验已经确定了两个结构相似的核小体结构域，SIN和LRS，所需的转录抑制在基因调控的SWI/SNF染色质重塑复合物或异染色质基因沉默，分别。这些结构域中的每一个由组蛋白H3和H4 L1和L2环组成，其在超螺旋位置（SHL）+/- 2.5（LRS）或SHL +/- 0.5（SIN）处形成DNA结合表面。在这里，我们表明，LRS结构域的改变不会导致SIN（-）表型，SIN结构域的破坏也不会导致核糖体DNA异染色质基因沉默（Lrs（-）表型）的损失。此外，而SIN结构域的破坏消除了体外核小体阵列的分子内折叠，LRS结构域的改变对体外染色质折叠没有影响。与这些不同之处相比，我们发现SIN和LRS结构域都需要招募Sir 2 p和Sir 4p端粒和沉默交配型基因座，这表明这两个表面都可以有助于异染色质的形成。我们的研究表明，结构相似的核小体表面在体内和体外提供不同的功能。
Genetic experiments have identified two structurally similar nucleosomal domains, SIN and LRS, required for transcriptional repression at genes regulated by the SWI/SNF chromatin remodeling complex or for heterochromatic gene silencing, respectively. Each of these domains consists of histone H3 and H4 L1 and L2 loops that form a DNA-binding surface at either superhelical location (SHL) +/- 2.5 (LRS) or SHL +/- 0.5 (SIN). Here we show that alterations in the LRS domain do not result in Sin(-) phenotypes, nor does disruption of the SIN domain lead to loss of ribosomal DNA heterochromatic gene silencing (Lrs(-) phenotype). Furthermore, whereas disruption of the SIN domain eliminates intramolecular folding of nucleosomal arrays in vitro, alterations in the LRS domain have no effect on chromatin folding in vitro. In contrast to these dissimilarities, we find that the SIN and LRS domains are both required for recruitment of Sir2p and Sir4p to telomeric and silent mating type loci, suggesting that both surfaces can contribute to heterochromatin formation. Our study shows that structurally similar nucleosomall surfaces provide distinct functionalities in vivo and in vitro.