NuMA influences higher order chromatin organization in human mammary epithelium
NuMA influences higher order chromatin organization in human mammary epithelium
复制标题
DOI：
10.1091/mbc.e06-06-0551
复制
发表时间：
2007-02-01
影响因子：
3.3
通讯作者：
Lelievre, Sophie A.
中科院分区：
文献类型：
--
作者：
Abad, Patricia C.;Lewis, Jason;Lelievre, Sophie A.
卷曲螺旋蛋白NuMA是有丝分裂纺锤体形成和稳定的重要贡献者。NuMA在核组织或基因调控中的潜在作用是由观察结果表明的，其核分布模式取决于细胞表型，并且它与转录因子相互作用和/或共定位。迄今为止，NuMA对核功能的确切贡献仍不清楚。以前，我们观察到，抗体诱导的NuMA分布在生长停滞和分化的乳腺上皮结构（腺泡）在三维培养触发腺泡分化的损失。在这里，我们表明，在乳腺上皮细胞中，NuMA存在于核基质和染色质隔室中。与染色质调节剂HPC 2共享序列相似性的NuMA的C末端的一部分的表达足以抑制腺泡分化，并且与对照细胞相比，导致NuMA、染色质标记物乙酰-H4和H4 K20 m以及脱氧核糖核酸酶I敏感性染色质区域的重新分布。在活腺泡细胞中，抗NuMA C末端抗体对NuMA分布的短期改变表明，NuMA和染色质组织的变化先于腺泡分化的丧失。这些发现表明NuMA通过影响染色质的组织在乳腺上皮分化中发挥作用。
The coiled-coil protein NuMA is an important contributor to mitotic spindle formation and stabilization. A potential role for NuMA in nuclear organization or gene regulation is suggested by the observations that its pattern of nuclear distribution depends upon cell phenotype and that it interacts and/or colocalizes with transcription factors. To date, the precise contribution of NuMA to nuclear function remains unclear. Previously, we observed that antibody-induced alteration of NuMA distribution in growth-arrested and differentiated mammary epithelial structures (acini) in three-dimensional culture triggers the loss of acinar differentiation. Here, we show that in mammary epithelial cells, NuMA is present in both the nuclear matrix and chromatin compartments. Expression of a portion of the C terminus of NuMA that shares sequence similarity with the chromatin regulator HPC2 is sufficient to inhibit acinar differentiation and results in the redistribution of NuMA, chromatin markers acetyl-H4 and H4K20m, and regions of deoxyribonuclease I-sensitive chromatin compared with control cells. Short-term alteration of NuMA distribution with anti-NuMA C-terminus antibodies in live acinar cells indicates that changes in NuMA and chromatin organization precede loss of acinar differentiation. These findings suggest that NuMA has a role in mammary epithelial differentiation by influencing the organization of chromatin.