Identification and characterization of the two isoforms of the vertebrate H2A.Z histone variant.
Identification and characterization of the two isoforms of the vertebrate H2A.Z histone variant.
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DOI：
10.1093/nar/gkq171
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发表时间：
2010-07
影响因子：
14.9
通讯作者：
Harata M
中科院分区：
文献类型：
--
作者：
Matsuda R;Hori T;Kitamura H;Takeuchi K;Fukagawa T;Harata M
组蛋白变体在基因组功能的表观遗传调控中起着重要作用。组蛋白变体H2A.Z在从酵母到脊椎动物的进化上是保守的，并且已经报道其对基因表达和绝缘以及染色体分离具有多种影响。最近在脊椎动物基因组中鉴定了两个编码H2A.Z的基因。然而，目前尚不清楚这些基因转录的蛋白质是否在功能上不同。为了解决这个问题，我们在鸡DT 40细胞中单独敲除每个基因。我们发现，两个不同的蛋白质，H2A.Z-1和H2A.Z-2，从这些基因产生的，这些蛋白质可以在一个长的SDS-PAGE凝胶分离。这两种异构体沉积到一个类似的程度由SRCAP染色质重塑复合物，这表明冗余的功能。然而，细胞缺乏任何一个的两种异构体表现出明显的细胞生长和基因表达的变化，这表明这两种异构体有不同的核小体稳定性和染色质结构的影响。这些发现提供了对H2A.Z基因产物的多种功能的分子基础的深入了解。
Histone variants play important roles in the epigenetic regulation of genome function. The histone variant H2A.Z is evolutionarily conserved from yeast to vertebrates, and it has been reported to have multiple effects upon gene expression and insulation, and chromosome segregation. Recently two genes encoding H2A.Z were identified in the vertebrate genome. However, it is not yet clear whether the proteins transcribed from these genes are functionally distinct. To address this issue, we knocked out each gene individually in chicken DT40 cells. We found that two distinct proteins, H2A.Z-1 and H2A.Z-2, were produced from these genes, and that these proteins could be separated on a long SDS–PAGE gel. The two isoforms were deposited to a similar extent by the SRCAP chromatin-remodeling complex, suggesting redundancy to their function. However, cells lacking either one of the two isoforms exhibited distinct alterations in cell growth and gene expression, suggesting that the two isoforms have differential effects upon nucleosome stability and chromatin structure. These findings provide insight into the molecular basis of the multiple functions of the H2A.Z gene products.
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影响因子：
9.8
作者：
Brickner DG;Cajigas I;Fondufe-Mittendorf Y;Ahmed S;Lee PC;Widom J;Brickner JH
通讯作者：
Brickner JH
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通讯作者：
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作者：
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