Organization of highly acetylated chromatin around sites of heterogeneous nuclear RNA accumulation
Organization of highly acetylated chromatin around sites of heterogeneous nuclear RNA accumulation
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DOI：
10.1091/mbc.9.9.2491
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发表时间：
1998-09-01
影响因子：
3.3
通讯作者：
Bazett-Jones, DP
中科院分区：
文献类型：
--
作者：
Hendzel, MJ;Kruhlak, MJ;Bazett-Jones, DP
在基因组的转录活性区域内发现的组蛋白是高度乙酰化的。此外，这些高度乙酰化的组蛋白具有非常短的半衰期。因此，组蛋白乙酰基转移酶和组蛋白脱乙酰基酶都必须在间期染色单体的常染色质区域内或附近富集。使用高度乙酰化的组蛋白H3的特异性抗体，我们已经调查了组织的转录活性和主管染色质以及核组蛋白乙酰转移酶和脱乙酰酶的活动。我们观察到高度乙酰化的染色质周围的细胞核周围的排斥和富集附近的染色质间颗粒簇（IGCs）。高度乙酰化的染色质被发现在灶中，可能反映了高度乙酰化的染色质组织成“染色丝”纤维。印度赤麂成纤维细胞核的透射电子显微镜副本表明，与IGC的周边相关的染色质保持相对浓缩，最常见于含有折叠超过30 nm的染色质的结构域。使用电子光谱成像，我们证明IGCs是核糖核蛋白颗粒的集群。单个颗粒包含折叠成单个颗粒的富含RNA的原纤维或球状区域。单个颗粒的定量分析表明，它们含有估计在1.5和>10 kb之间的可变量的RNA。我们认为染色质间颗粒是核内含有RNA的异质颗粒，其中一些可能是由附近的染色质转录产生的前mRNA。IGC和周围的染色质之间的中间区被描述为包含有可能提供特异性的IGC附近的序列的本地化的因素。
Histones found within transcriptionally competent and active regions of the genome are highly acetylated. Moreover, these highly acetylated histones have very short half-lives. Thus, both histone acetyltransferases and histone deacetylases must enrich within or near these euchromatic regions of the interphase chromatids. Using an antibody specific for highly acetylated histone H3, we have investigated the organization of transcriptionally active and competent chromatin as well as nuclear histone acetyltransferase and deacetylase activities. We observe an exclusion of highly acetylated chromatin around the periphery of the nucleus and an enrichment near interchromatin granule clusters (IGCs). The highly acetylated chromatin is found in foci that may reflect the organization of highly acetylated chromatin into "chromonema" fibers. Transmission electron microscopy copy of Indian muntjac fibroblast cell nuclei indicates that the chromatin associated with the periphery of IGCs remains relatively condensed, most commonly found in domains containing chromatin folded beyond 30 nm. Using electron spectroscopic imaging, we demonstrate that IGCs are clusters of ribonucleoprotein particles. The individual granules comprise RNA-rich fibrils or globular regions that fold into individual granules. Quantitative analysis of individual granules indicates that they contain variable amounts of RNA estimated between 1.5 and >10 kb. We propose that interchromatin granules are heterogeneous nuclear RNA-containing particles, some of which may be pre-mRNA generated by nearby transcribed chromatin. An intermediary zone between the IGC and surrounding chromatin is described that contains factors with the potential to provide specificity to the localization of sequences near IGCs.