Centromeric transcription has been shown to play an important role in centromere functions. However, lack of approaches to specifically manipulate centromeric transcription calls into question that the proposed functions are a direct consequence of centromeric transcription. By monitoring nascent RNAs, we found that several transcriptional inhibitors exhibited distinct, even opposing, efficacies on the suppression of ongoing gene and centromeric transcription in human cells, whereas under the same conditions, total centromeric RNAs were changed to a lesser extent. The inhibitor suppressing ongoing centromeric transcription weakened centromeric cohesion, whereas the inhibitor increasing ongoing centromeric transcription strengthened centromeric cohesion. Furthermore, expression of CENP-B DNA-binding domain or CENP-B knockdown moderately increased centromeric transcription without altering gene transcription; as a result, centromeric cohesion was accordingly strengthened. Targeting of the Kox1-KRAB domain with CENP-B DB to centromeres specifically decreased centromeric transcription and weakened centromeric cohesion. Thus, based on these findings, we propose that a major function of centromeric transcription is to maintain centromeric cohesion in human cells.

中文翻译：

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着丝粒转录在人类细胞中维持着着丝粒的内聚力。

着丝粒转录已显示在着丝粒功能中起重要作用。然而，缺乏特异性操纵着丝粒转录的方法的不足使人们怀疑所提出的功能是着丝粒转录的直接结果。通过监测新生RNA，我们发现几种转录抑制剂在抑制人类细胞中正在进行的基因和着丝粒转录方面表现出独特的，甚至相反的功效，而在相同条件下，总着丝粒RNA的变化程度较小。抑制正在进行的着丝粒转录的抑制剂减弱了着丝粒的内聚力，而抑制剂增加正在进行的着丝粒转录的增强了着丝粒的内聚力。此外，CENP-B DNA结合结构域的表达或CENP-B敲低的表达适度增加着丝粒转录，而不会改变基因转录；结果，着丝粒的内聚力相应地增强了。带有CENP-B DB的Kox1-KRAB结构域靶向着丝粒的作用特别是降低了着丝粒的转录并减弱了着丝粒的内聚力。因此，基于这些发现，我们提出着丝粒体转录的主要功能是维持人细胞中着丝粒体的内聚力。