Heterochromatin biology

我们正在研究维持本构异色区在凝聚形式的机制。为此，我们最初使用了位于鸡β -珠蛋白位点上游的一个很好表征的16kb异染色质片段。在其他已发表的研究中，我们测量了该片段的流体动力学特性，这是脊椎动物基因组中很大一部分的典型特征，如果不加以调节，它有可能以一种有害于细胞功能的方式沉默相邻基因。我们发现压缩结构的维持与该区域的低水平转录相耦合，并且通过使用组蛋白去乙酰化酶抑制剂（TSA）来提高组蛋白乙酰化水平显着增加转录。我们想知道Dicer/Argonaute依赖性机制是否参与了这个异色区域的形成。我们发现，siRNA对Dicer的耗损导致染色质结构的开放，这与TSA处理后观察到的情况非常相似。此外，Ago2以dicer依赖的方式结合到该区域。

We are studying the mechanisms that maintain constitutive heterochromatic regions in a condensed form. For this purpose we originally used a well characterized 16 kb heterochromatin segment located upstream of the chicken beta globin locus. In other published studies we have measured the hydrodynamic properties of this fragment, which is typical of a large proportion of vertebrate genomes, and which has the potential if unregulated to silence adjacent genes in a manner deleterious to cellular function. We found that maintenance of the condensed structure is coupled to low level transcription in the region, and that elevation of levels of histone acetylation by use of histone deacetylase inhibitors (TSA) markedly increases transcription. We asked whether Dicer/Argonaute dependent mechanisms could be involved in formation of this heterochromatic region. We found that depletion of Dicer by siRNA resulted in opening of the condensed chromatin structure much as what was observed following TSA treatment. Furthermore, Ago2 is bound to this region in a Dicer-dependent manner. We have now investigated the binding of Ago2 to the ribosomal gene repeats in the human erythroid cell line, K562. We find that human AGO2 is localized to the chromatin of the rRNA gene coding region. This localization is mediated through interaction with RNAs that affect rRNA modification.