Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N.

Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N.
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DOI:
10.1038/ncb1899
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发表时间:
2009-07
影响因子:
21.3
通讯作者:
Straight, Aaron F.
Straight, Aaron F.
中科院分区:
生物学1区
文献类型:
--
作者:
Carroll, Christopher W.;Silva, Mariana C. C.;Godek, Kristina M.;Jansen, Lars E. T.;Straight, Aaron F.

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着丝粒是特殊的染色体区域,在有丝分裂期间指导动粒组装。CENP - A是一种仅存在于着丝粒核小体中的组蛋白H3变体,被认为是一种决定着丝粒特性的表观遗传标记。在此我们确定关键的着丝粒蛋白CENP - N是第一种选择性结合CENP - A核小体而非H3核小体的蛋白。CENP - N以不依赖DNA序列的方式结合CENP - A核小体,但不结合可溶性的CENP - A/H4四聚体。CENP - N中降低其对CENP - A核小体亲和力的突变会导致CENP - N定位缺陷,并对着丝粒上CENP - H、CENP - I和CENP - K的募集产生显性效应。用小干扰RNA(siRNA)消耗CENP - N会导致类似的着丝粒组装缺陷,并导致新生CENP - A组装入着丝粒染色质减少。这些数据表明,CENP - N解读CENP - A核小体中编码的信息,并将着丝粒功能和延续所需的其他蛋白质募集到着丝粒染色质。
Centromeres are specialized chromosomal domains that direct kinetochore assembly during mitosis. CENP-A, a histone H3-variant present exclusively in centromeric nucleosomes, is thought to act as an epigenetic mark that specifies centromere identity. Here we identify the essential centromere protein CENP-N as the first protein to selectively bind CENP-A nucleosomes but not H3 nucleosomes. CENP-N bound CENP-A nucleosomes in a DNA-sequence independent manner but did not bind soluble CENP-A/H4 tetramers. Mutations in CENP-N that reduced the affinity of CENP-N for CENP-A nucleosomes caused defects in CENP-N localization and had dominant effects on the recruitment of CENP-H, CENP-I and CENP-K to centromeres. Depletion of CENP-N with siRNA’s led to similar centromere assembly defects and resulted in reduced assembly of nascent CENP-A into centromeric chromatin. These data suggest that CENP-N interprets the information encoded within CENP-A nucleosomes and recruits to centromeric chromatin other proteins required for centromere function and propagation.
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