SWI/SNF-like chromatin remodeling factor Fun30 supports point centromere function in S. cerevisiae.
SWI/SNF-like chromatin remodeling factor Fun30 supports point centromere function in S. cerevisiae.
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DOI：
10.1371/journal.pgen.1002974
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发表时间：
2012-09
期刊：
影响因子：
4.5
通讯作者：
Varga-Weisz P
中科院分区：
文献类型：
--
作者：
Durand-Dubief M;Will WR;Petrini E;Theodorou D;Harris RR;Crawford MR;Paszkiewicz K;Krueger F;Correra RM;Vetter AT;Miller JR;Kent NA;Varga-Weisz P
芽殖酵母着丝粒是序列定义的点着丝粒，与许多其他生物不同，它不嵌入异染色质中。在这里，我们表明，Fun 30，一个知之甚少的SWI/SNF样染色质重塑因子在人类中保守，促进点着丝粒功能，通过正确的染色质结构在着丝粒的形成。我们对Fun 30的全基因组结合和核小体定位特性的测定表明，这种酶在着丝粒上始终富集，并且大多数CEN在侧翼核小体位置和/或CEN核心微球菌核酸酶可及性方面显示出Fun 30依赖性变化。Fun 30缺失导致组蛋白变体Htz 1在全基因组范围内占据的缺陷，包括在大多数着丝粒处和周围。FUN 30与编码组蛋白H3的着丝粒特异性变体的CSE 4在遗传上相互作用，并抵消通过着丝粒转录对染色体分离的有害影响，并抑制着丝粒CEN 3上的转录噪音。以前的工作已经表明，在异染色质组装中需要Fun 30的裂殖酵母和哺乳动物同源物。由于芽殖酵母中的着丝粒不嵌入异染色质中，我们的研究结果表明Fun 30通过促进正确的染色质结构在着丝粒染色质中发挥直接作用。着丝粒是染色质结构所必需的，为有丝分裂纺锤体提供结合平台。着丝粒结构或功能的缺陷可导致染色体错误分离或染色体断裂。这反过来又会导致后生动物的癌症。着丝粒由含有组蛋白H3变体CENP-A（也称为CenH 3或芽殖酵母中的Cse 4）的特化染色质定义，并且着丝粒上的转录受到严格控制。芽殖酵母着丝粒由含有必需Cse 4的单个核小体组成。这些特化的着丝粒核小体中的一个的丢失可导致在有丝分裂期间染色体错误分离，随后细胞死亡。我们提供的证据表明，能量依赖性染色质重塑因子Fun 30支持忠实的染色体分离，特别是当着丝粒结构受到Cse 4突变或通过着丝粒强制转录的挑战时，这会破坏着丝粒结构。我们发现，Fun 30结合到着丝粒和Fun 30的损失导致在着丝粒染色质的各种缺陷，这表明Fun 30在促进正常的着丝粒功能的直接作用。我们的分析表明，Fun 30影响核小体定位在许多基因组位点，包括着丝粒，是所需的组蛋白变体Htz 1的正常占用。在没有Fun 30的情况下，我们检测到通过着丝粒的转录增加。我们认为Fun 30的一个重要功能是限制着丝粒上的转录。
Budding yeast centromeres are sequence-defined point centromeres and are, unlike in many other organisms, not embedded in heterochromatin. Here we show that Fun30, a poorly understood SWI/SNF-like chromatin remodeling factor conserved in humans, promotes point centromere function through the formation of correct chromatin architecture at centromeres. Our determination of the genome-wide binding and nucleosome positioning properties of Fun30 shows that this enzyme is consistently enriched over centromeres and that a majority of CENs show Fun30-dependent changes in flanking nucleosome position and/or CEN core micrococcal nuclease accessibility. Fun30 deletion leads to defects in histone variant Htz1 occupancy genome-wide, including at and around most centromeres. FUN30 genetically interacts with CSE4, coding for the centromere-specific variant of histone H3, and counteracts the detrimental effect of transcription through centromeres on chromosome segregation and suppresses transcriptional noise over centromere CEN3. Previous work has shown a requirement for fission yeast and mammalian homologs of Fun30 in heterochromatin assembly. As centromeres in budding yeast are not embedded in heterochromatin, our findings indicate a direct role of Fun30 in centromere chromatin by promoting correct chromatin architecture. Centromeres are essential to chromatin structures, providing a binding platform for the mitotic spindle. Defects in centromere structure or function can lead to chromosome missegregation or chromosome breakage. This, in turn, can cause cancer in metazoans. Centromeres are defined by specialized chromatin that contains the histone H3 variant CENP-A (also called CenH3, or Cse4 in budding yeast), and transcription over centromeres is tightly controlled. Budding yeast centromeres are composed of a single nucleosome containing the essential Cse4. Loss of one of these specialized centromeric nucleosomes can lead to chromosome missegregation during mitosis followed by cell death. We provide evidence that energy-dependent chromatin remodeling factor Fun30 supports faithful chromosome segregation, especially when centromere structure is challenged by mutation of Cse4 or by forced transcription through centromeres, which disrupt centromere structure. We show that Fun30 binds to centromeres and that loss of Fun30 leads to various defects in centromere chromatin, suggesting a direct role for Fun30 in promoting normal centromere function. Our analysis shows that Fun30 affects nucleosome positioning at many genomic sites, including centromeres, and is required for normal occupancy of histone variant Htz1. In the absence of Fun30, we detect an increase in transcription through centromeres. We suggest that an important function of Fun30 is to limit transcription over centromeres.
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影响因子：
64.5
作者：
Floer, Monique;Wang, Xin;Ptashne, Mark
通讯作者：
Ptashne, Mark
影响因子：
10.5
作者：
D'Ambrosio, Claudio;Schmidt, Christine Katrin;Uhlmann, Frank
通讯作者：
Uhlmann, Frank
影响因子：
14.9
作者：
Castano, IB;HeathPagliuso, S;Christman, MF
通讯作者：
Christman, MF
Snf2 同源物 Fun30 充当同型二聚体 ATP 依赖性染色质重塑酶。
DOI：
10.1074/jbc.m109.082149
发表时间：
2010-03-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Awad S;Ryan D;Prochasson P;Owen-Hughes T;Hassan AH
通讯作者：
Hassan AH
影响因子：
4
作者：
Grewal, Shiv I. S.
通讯作者：
Grewal, Shiv I. S.