Pash J M, Alfonso P J, Bustin M
Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1993 Jun 25;268(18):13632-8.
High mobility group (HMG) 14 is a ubiquitous chromosomal protein that binds specifically to nucleosomal DNA and may be involved in a process that confers distinct properties to the chromatin structure of transcriptionally active genes. To explore the involvement of this protein in regulation of gene expression, we studied the effect of aberrant expression of HMG-14 protein on cellular differentiation. We produced stably transfected C2C12 mouse myoblasts expressing the human HMG-14 protein under the control of the mouse mammary tumor virus promoter. Transformed colonies retained their potential do differentiate into myotubes. Induction of human HMG-14 expression by dexamethasone inhibited the myogenic process. Revertant colonies, which lost the ability to express human HMG-14, regained the ability to differentiate into myotubes. Inhibition of myoblast differentiation by aberrantly expressed HMG-14 correlated with down-regulation of myogenic determination factors. The results suggest that proper cellular differentiation requires regulated expression of HMG-14 protein and are consistent with the possibility that this protein may be involved in gene regulation.
高迁移率族(HMG)14是一种普遍存在的染色体蛋白,它能特异性地结合核小体DNA,可能参与赋予转录活性基因染色质结构独特性质的过程。为了探究这种蛋白在基因表达调控中的作用,我们研究了HMG - 14蛋白异常表达对细胞分化的影响。我们构建了稳定转染的C2C12小鼠成肌细胞,其在小鼠乳腺肿瘤病毒启动子的控制下表达人HMG - 14蛋白。转化后的菌落保留了分化为肌管的潜能。地塞米松诱导人HMG - 14表达抑制了成肌过程。失去表达人HMG - 14能力的回复菌落重新获得了分化为肌管的能力。异常表达的HMG - 14对成肌细胞分化的抑制与成肌决定因子的下调相关。结果表明,正常的细胞分化需要HMG - 14蛋白的调控表达,并且与这种蛋白可能参与基因调控的可能性一致。