Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes.
Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes.
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DOI：
10.1186/1471-2164-10-610
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发表时间：
2009-12-16
期刊：
影响因子：
4.4
通讯作者：
Cui L
中科院分区：
文献类型：
--
作者：
Westenberger SJ;Cui L;Dharia N;Winzeler E;Cui L
组蛋白的表观遗传修饰和染色质结构的调节与恶性疟原虫毒力基因家族的调节有关。为了更好地理解染色质介导的基因调控，我们使用高密度寡核苷酸微阵列在体外红细胞内发育周期（IDC）的三个时间点绘制恶性疟原虫整个基因组中核小体的位置和富集。我们使用未修饰的组蛋白H4抗体进行核小体结合DNA的染色质免疫沉淀。我们观察到普遍较低的核小体占用的基因间区域和较高的蛋白质编码区的占用。在合同的整体小波动的核小体占据在大多数编码区在整个IDC，亚端粒基因编码的表面蛋白，如var和rif，以及一些核心染色体基因，如转录因子，染色质结构的变化很大。端粒具有基因组中核小体占有率最高的区域，并且在端粒阶段也表现出较大的变化，具有较高的核小体占有率。虽然许多这些亚端粒基因先前被证明是由H3K9三甲基化修饰，我们还确定了一些管家基因在核心染色体区域，显示广泛的染色质结构的变化，但不包含这种修饰。tRNA和基础转录因子基因在任何时候都表现出较低的核小体占有率，这表明开放的染色质结构可能允许组成性高水平的表达。一般来说，核小体占有率与稳态mRNA水平不相关。几个var基因是例外：var基因的表达水平最高，核小体占有率最低，选择寄生虫的var2CSA表达导致较低的核小体占有率在var2CSA基因座。我们确定了基因间区域的无核小体区域，可能作为转录起始位点或转录因子结合位点。使用核小体占据数据作为基线，我们进一步绘制了H3K9乙酰化的全基因组富集，并检测到该标记在基因间区域的普遍富集。这些核小体富集变化的数据增加了我们对染色质结构对基因表达调控的影响的理解。组蛋白通常在编码区富集，而在基因间区相对贫乏。组蛋白富集模式允许鉴定新的推定基因编码区。大多数基因没有显示染色质结构和稳态mRNA水平之间的相关性，表明其他调控机制的主导作用。我们提出了一个全基因组的核小体占有率图，这可以作为一个参考，为未来的实验组蛋白修饰映射。
Epigenetic modifications of histones and regulation of chromatin structure have been implicated in regulation of virulence gene families in P. falciparum. To better understand chromatin-mediated gene regulation, we used a high-density oligonucleotide microarray to map the position and enrichment of nucleosomes across the entire genome of P. falciparum at three time points of the intra-erythrocytic developmental cycle (IDC) in vitro. We used an unmodified histone H4 antibody for chromatin immunoprecipitation of nucleosome-bound DNA. We observed generally low nucleosomal occupancy of intergenic regions and higher occupancy of protein coding regions. In contract to the overall small fluctuation of nucleosomal occupancy in most coding regions throughout the IDC, subtelomeric genes encoding surface proteins such as var and rif, as well as some core chromosomal genes such as transcription factors, showed large changes in chromatin structure. Telomeres harbored a region with the highest nucleosomal occupancy of the genome and also exhibited large changes with higher nucleosomal occupancy at schizont stages. While many of these subtelomeric genes were previously shown to be modified by H3K9 trimethylation, we also identified some housekeeping genes in core chromosome regions that showed extensive changes in chromatin structure but do not contain this modification. tRNA and basal transcription factor genes showed low nucleosomal occupancy at all times, suggesting of an open chromatin structure that might be permissive for constitutively high levels of expression. Generally, nucleosomal occupancy was not correlated with the steady-state mRNA levels. Several var genes were exceptions: the var gene with the highest expression level showed the lowest nucleosomal occupancy, and selection of parasites for var2CSA expression resulted in lower nucleosomal occupancy at the var2CSA locus. We identified nucleosome-free regions in intergenic regions that may serve as transcription start sites or transcription factor binding sites. Using the nucleosomal occupancy data as the baseline, we further mapped the genome-wide enrichment of H3K9 acetylation and detected general enrichment of this mark in intergenic regions. These data on nucleosome enrichment changes add to our understanding of the influence of chromatin structure on the regulation of gene expression. Histones are generally enriched in coding regions, and relatively poor in intergenic regions. Histone enrichment patterns allow for identification of new putative gene-coding regions. Most genes do not show correlation between chromatin structure and steady-state mRNA levels, indicating the dominant roles of other regulatory mechanisms. We present a genome-wide nucleosomal occupancy map, which can be used as a reference for future experiments of histone modification mapping.
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影响因子：
12.3
作者：
Dharia NV;Sidhu AB;Cassera MB;Westenberger SJ;Bopp SE;Eastman RT;Plouffe D;Batalov S;Park DJ;Volkman SK;Wirth DF;Zhou Y;Fidock DA;Winzeler EA
通讯作者：
Winzeler EA
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
30.8
作者：
Ioshikhes, Ilya P.;Albert, Istvan;Pugh, B. Franklin
通讯作者：
Pugh, B. Franklin
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
影响因子：
2.1
作者：
Gopalakrishnan, Anusha M.;Nyindodo, Lilian A.;Lopez-Estrano, Carlos
通讯作者：
Lopez-Estrano, Carlos