Specific and conserved sequences in D-melanogaster and C-elegans lamins and histone H2A mediate the attachment of lamins to chromosomes
Specific and conserved sequences in D-melanogaster and C-elegans lamins and histone H2A mediate the attachment of lamins to chromosomes
复制标题
DOI：
10.1242/jcs.03325
复制
发表时间：
2007-01-01
影响因子：
4
通讯作者：
Gruenbaum, Yosef
中科院分区：
文献类型：
--
作者：
Mattout, Anna;Goldberg, Michal;Gruenbaum, Yosef
核纤层蛋白和染色质之间的密切联系被认为可以调节高级染色质组织。先前的研究已经绘制了果蝇核纤层蛋白 Dm(0) 尾部结构域中杆结构域和 Ig 折叠之间的区域，该区域通过组蛋白 H2A/H2B 二聚体在体外结合染色质。该区域包含进化上保守的核定位信号（NLS）KRKR，以及由氨基酸TRAT组成的序列。在这里，我们表明核纤层蛋白 Dm(0) 与染色质的结合需要 NLS 和 TRAT 序列。用带负电荷的残基取代 TRAT 序列中的任一苏氨酸残基会降低核纤层蛋白 Dm(0) 与染色质的结合，表明这种结合可以通过磷酸化来调节。核纤层蛋白 Dm(0) 和线虫 Ce-核纤层蛋白在体外均直接与组蛋白 H2A 结合，并且这种结合需要 NLS。组蛋白 H2A 的氨基和羧基尾部结构域对于与核纤层蛋白 Dm(0) 的结合都是必需的，但还不够；只有含有两个组蛋白 H2A 尾部结构域的多肽才能有效结合核纤层蛋白 Dm(0)。总而言之，这些结果表明核纤层蛋白 Dm(0) 和组蛋白 H2A 中的特定残基介导体内核纤层与染色体的附着，这可能对理解核纤层蛋白病具有影响。
The intimate association between nuclear lamins and chromatin is thought to regulate higher order chromatin organization. Previous studies have mapped a region between the rod domain and the Ig fold in the tail domain of Drosophila melanogaster lamin Dm(0), which binds chromatin in vitro via the histone H2A/H2B dimer. This region contains an evolutionarily conserved nuclear localization signal (NLS) KRKR, and a sequence composed of the amino acids TRAT. Here we show that binding of lamin Dm(0) to chromatin requires both NLS and TRAT sequences. Substituting either of the threonine residues in the TRAT sequence with negatively charged residues decreases the binding of lamin Dm(0) to chromatin, indicating that this binding could be regulated by phosphorylation. Both lamin Dm(0) and C. elegans Ce-lamin bind directly to histone H2A in vitro and this binding requires the NLS. The amino and carboxyl tail domains of histone H2A are each essential, but not sufficient, for binding to lamin Dm(0); only a polypeptide containing both histone H2A tail domains binds efficiently to lamin Dm(0). Taken together, these results suggest that specific residues in lamin Dm(0) and histone H2A mediate the attachment of the nuclear lamina to chromosomes in vivo, which could have implications on the understanding of laminopathic diseases.