Centre for Cellular and Molecular Biology, (Council of Scientific and Industrial Research), Uppal Road, Hyderabad-500007, India.
Epigenetics Chromatin. 2009 Mar 16;2(1):4. doi: 10.1186/1756-8935-2-4.
Genome-wide mappings of nucleosome occupancy in different species have shown presence of well-positioned nucleosomes. While the DNA sequences may help decide their locations, the observed positions in vivo are end-results of chromatin remodeling, the state of gene activity and binding of the sequence-specific factors to the DNA, all of which influence nucleosome positions. Thus, the observed nucleosome locations in vivo do not reflect the true contribution of DNA sequence to the mapped position. Moreover, the naturally occurring nucleosome-positioning sequences are known to guide multiple translational positionings.
We show that yeast SNR6, a gene transcribed by RNA polymerase III, constitutes nucleosome-positioning sequence. In the absence of a chromatin remodeler or any factor binding, the gene sequence confers a unique rotational phase to nucleosomes in the gene region, and directs assembly of several translationally positioned nucleosomes on approximately 1.2 kb DNA from the gene locus, including the short approximately 250 bp gene region. Mapping of all these gene sequence-directed nucleosome positions revealed that the array of nucleosomes in the gene upstream region occupy the same positions as those observed in vivo but the nucleosomes on the gene region can be arranged in three distinct registers. Two of these arrangements differ from each other in the position of only one nucleosome, and match with the nucleosome positions on the gene in repressed and active states in vivo, where the gene-specific factor is known to occupy the gene in both the states. The two positions are interchanged by an ATP-dependent chromatin remodeler in vivo. The third register represents the positions which block the access of the factor to the gene promoter elements.
On a gene locus, multiple nucleosome positions are directed by a gene sequence to provide a pool of possibilities, out of which the preferred ones are selected by the chromatin remodeler and transcription factor of the gene under different states of activity of the gene.
在不同物种中进行的核小体占据基因组图谱显示,核小体的位置是固定的。虽然 DNA 序列可能有助于决定它们的位置,但在体内观察到的位置是染色质重塑、基因活性状态以及序列特异性因子与 DNA 结合的结果,所有这些都影响核小体的位置。因此,在体内观察到的核小体位置并不反映 DNA 序列对映射位置的真实贡献。此外,已知天然存在的核小体定位序列可指导多个翻译定位。
我们表明,酵母 SNR6,一种由 RNA 聚合酶 III 转录的基因,构成核小体定位序列。在没有染色质重塑因子或任何因子结合的情况下,该基因序列赋予基因区域内核小体独特的旋转相位,并指导在大约 1.2 kb 的 DNA 上组装几个翻译定位的核小体,包括短约 250 bp 的基因区域。所有这些基因序列指导的核小体位置的映射表明,基因上游区域的核小体阵列占据了与体内观察到的相同位置,但基因区域的核小体可以排列成三个不同的寄存器。其中两个排列在只有一个核小体的位置上彼此不同,并且与体内基因在抑制和激活状态下的核小体位置相匹配,其中已知基因特异性因子在两种状态下都占据基因。体内的 ATP 依赖性染色质重塑因子将这两个位置互换。第三个寄存器代表阻止因子进入基因启动子元件的位置。
在基因座上,基因序列指导多个核小体位置,提供了一个可能性的池,其中由染色质重塑因子和基因的转录因子在基因不同活性状态下选择首选位置。