Genomic size of CENP-A domain is proportional to total alpha satellite array size at human centromeres and expands in cancer cells.
Genomic size of CENP-A domain is proportional to total alpha satellite array size at human centromeres and expands in cancer cells.
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CENP-A结构域的基因组大小与人centromeres的总α卫星阵列大小成正比，并在癌细胞中扩展。
DOI：
10.1007/s10577-011-9208-5
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发表时间：
2011-05
影响因子：
2.6
通讯作者：
Sullivan, Beth A.
中科院分区：
文献类型：
--
作者：
Sullivan, Lori L.;Boivin, Christopher D.;Mravinac, Brankica;Song, Ihn Young;Sullivan, Beth A.
人类着丝粒包含多个兆酶大小的α卫星DNA阵列，这是一个基于串联排列的171bp单体的卫星DNA重复序列家族。着丝粒特异性组蛋白CENP-A在初级缩窄内组装在α卫星DNA上，但不沿着其整个长度延伸。据估计，CENP-A结构域延伸超过1500-2000kb的α卫星DNA。然而，这些估计没有考虑到同源染色体和不同染色体上α卫星阵列大小的个体间差异。我们定义了不同个体在人类X染色体和Y染色体上的CENP-A染色质的基因组距离。CENP-A染色质在不同染色体上占据不同的基因组间隔，但尽管染色体间和个体间阵列大小存在差异，但CENP-A占α卫星DNA总大小的比例保持一致。当过表达CENP-A和通过破坏肿瘤抑制蛋白Rb和染色质之间的相互作用转化原代细胞时，观察到α卫星阵列大小与CENP-A结构域大小之比的变化。我们的数据支持着丝粒结构域组织模型，在该模型中，CENP-A染色质的基因组限制在不同的人类染色体上是不同的，这意味着α卫星阵列的大小比染色体大小更能预测CENP-A的整合。此外，我们的研究结果还表明，癌症转化和着丝异染色质的数量对与CENP-A染色质相关的α卫星的数量有显著影响。
Human centromeres contain multi-megabase-sized arrays of alpha satellite DNA, a family of satellite DNA repeats based on a tandemly arranged 171bp monomer. The centromere-specific histone protein CENP-A is assembled on alpha satellite DNA within the primary constriction, but does not extend along its entire length. CENP-A domains are estimated to extend over 1500-2000kb of alpha satellite DNA. However, these estimates do not take into account inter-individual variation in alpha satellite array sizes on homologous chromosomes and among different chromosomes. We defined the genomic distance of CENP-A chromatin on human chromosomes X and Y from different individuals. CENP-A chromatin occupied different genomic intervals on different chromosomes, but despite inter-chromosomal and inter-individual array size variation, the ratio of CENP-A to total alpha satellite DNA size remained consistent. Changes in the ratio of alpha satellite array size to CENP-A domain size were observed when CENP-A was over-expressed and when primary cells were transformed by disrupting interactions between the tumor suppressor protein Rb and chromatin. Our data support a model for centromeric domain organization in which the genomic limits of CENP-A chromatin varies on different human chromosomes, and imply that alpha satellite array size is a more prominent predictor of CENP-A incorporation than chromosome size. In addition, our results also suggest that cancer transformation and amounts of centromeric heterochromatin have notable effects on the amount of alpha satellite that is associated with CENP-A chromatin.
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影响因子：
37.3
作者：
Amato A;Schillaci T;Lentini L;Di Leonardo A
通讯作者：
Di Leonardo A
影响因子：
7
作者：
Lo, AWI;Liao, GCC;Choo, KHA
通讯作者：
Choo, KHA
DOI：
10.1073/pnas.0507947103
发表时间：
2006-03-14
影响因子：
11.1
作者：
Lam, AL;Boivin, CD;Sullivan, BA
通讯作者：
Sullivan, BA
影响因子：
4.4
作者：
MAHTANI, MM;WILLARD, HF
通讯作者：
WILLARD, HF
影响因子：
3.7
作者：
Mravinac, Brankica;Sullivan, Lori L.;Sullivan, Beth A.
通讯作者：
Sullivan, Beth A.