The transcription factor B-Myb is essential for S-phase progression and genomic stability in diploid and polyploid megakaryocytes
The transcription factor B-Myb is essential for S-phase progression and genomic stability in diploid and polyploid megakaryocytes
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DOI：
10.1242/jcs.02870
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发表时间：
2006-04-15
影响因子：
4
通讯作者：
Frampton, J
中科院分区：
文献类型：
--
作者：
García, P;Frampton, J
细胞周期调控的Myb家族转录因子B-Myb在许多二倍体细胞类型的S期是至关重要的。我们已经研究了B-Myb在巨核细胞分化中的表达和功能，在此期间，细胞从二倍体发展到多倍体状态。与大多数造血细胞的终末分化（在此期间B-myb迅速下调）相反，巨核细胞的分化伴随着持续的B-myb RNA和蛋白质表达。在巨核细胞系中B-Myb的过表达导致进入S期的细胞数量增加，并且在诱导分化后，细胞内复制活跃的比例增加。相比之下，使用短干扰（si）RNA降低B-Myb水平会导致正常和内复制DNA合成期间S期进程的下降。这种效应与细胞核内DNA复制起始的异常定位和有丝分裂中细胞比例的增加相关。染色体断裂和其他畸变，包括染色单体更短、更厚、端对端融合和染色单体丢失，表明B-Myb活性降低也与结构性染色体不稳定有关。
The cell-cycle-regulated Myb-family transcription factor B-Myb is crucial during S phase in many diploid cell types. We have examined the expression and function of B-Myb in megakaryocytic differentiation, during which cells progress from a diploid to a polyploid state. In contrast to terminal differentiation of most haematopoietic cells, during which B-myb is rapidly downregulated, differentiation of megakaryocytes is accompanied by continued B-myb RNA and protein expression. Overexpression of B-Myb in a megakaryoblastic cell line resulted in an increase in the number of cells entering S phase and, upon induction of differentiation, the fraction of cells actively endoreplicating increased. By contrast, reduction of B-Myb levels using short interfering (si) RNA resulted in a decline in S-phase progression during both normal and endoreplicative DNA synthesis. This effect correlated with aberrant localisation of initiation of DNA replication within the nucleus and an increased fraction of cells in mitosis. Chromosomal fragmentation and other aberrations, including shorter, thicker chromatids, end-to-end fusion, and loss of a chromatid, suggest that reduced B-Myb activity is also associated with structural chromosomal instability.