Written by Professor James Davie,University of Manitoba, Canada

The nucleus produces an array of protein-coding and non-protein coding (nc)RNAs. There is growing appreciation and excitement in the role of the ncRNA in genome organization and function. ncRNA may have a role as genome organizing architectural factors of transcribed chromosomal domains (1, 2）和/或具有功能性作用，例如来自增强子（ERNAS）的NCRNA（ERNAS）（ERNAS）（3). Microinjection of RNase A into the nucleus of mammalian cells resulted in rearrangement of chromatin distribution with aggregation of chromatin at the nuclear periphery. This is a rather harsh treatment but it does make the case that nuclear RNA plays a role in the organization of the genome.

一类长NCRNA（LNCRNA）与蛋白质编码基因不重叠并激活转录，被称为NCRNA激活（4). Interestingly, knockdown of a ncRNA-activating specifically attenuated the expression of a “nearby” protein-coding gene; the median distance of a ncRNA-activating to the impacted protein-coding gene was over 100 kb in mammalian cells (4). A recent report shows that ncRNA-activating binds to mediator, a large multiprotein transcriptional coactivator (5).

Active enhancers produce eRNA which may play a role in the interaction between the enhancer and the promoter and the transcription of the nearby gene (3). These transcripts appear to be quite labile, and thus RNA sequencing may or may not detect these transcripts. One of the preferred methods to detect eRNA is a method described by Dr. John Lis and colleagues (6) called GRO-seq (global nuclear run-on coupled with massively parallel sequencing). It has been proposed that the eRNAs regulate transcription by promoting chromatin accessibility and RNAPII recruitment: processes that are required for the stabilization of enhancer-promoter interactions. Others argue that an interaction between the enhancer and promoter is required to produce eRNA. Regardless, it will be interesting to find out which epigenetic modifiers are associated with the eRNAs.

有越来越多的证据表明，与核RNA结合的染色质修饰剂和重塑剂在确定沿染色质的翻译后修饰位置方面起着关键作用（有关最近的评论，请参见（请参见（见）4、7、8)). Our interest in the RNA world peaked when we found that histone deacetylases (HDACs) and lysine acetyltransferases (KATs) were associated with the newly synthesized RNA (9). In our chromatin immunoprecipitation (ChIP) assays, we found that histone deacetylases appeared to be associated with the coding regions of genes. But if the cross-linked chromatin fragments were digested with RNase A before the immunoprecipitation with the HDAC antibodies, the interaction of the HDAC and coding region of the transcribed gene was lost. Similar observations have been made with splicing factors. This certainly raised a cautionary flag when interpreting results from ChIP assays.

HDAC和KAT与RNA没有直接相互作用，而是与参与前MRNA剪接的RNA结合蛋白结合。看来这些酶从前MRNA到催化附近染色质编码区的动态组蛋白乙酰化。

But not all nucleosomes are equal. In agreement with other reports (10, 11），我们发现具有H3K4甲基化标记的核小体（H3K4ME3）是选择性参与动态乙酰化的核小体。在这些研究过程中，内外外显子的长度大约为一个核小体，即147个碱基对。如果是髓样细胞白血病序列1（MCL1) gene, a dynamically acetylated H3K4me3 nucleosome is planted on the alternative exon 2. Thus when theMCL1RNA结合的组蛋白脱乙酰基酶的活性被抑制，外显子2核小体乙酰化水平峰值峰值，导致变化回到MCL1RNA by altering its splicing. I suppose it comes down to location, location, location.

参考：

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