Ghosh A K, Steele R, Ray R B
Department of Pathology, Saint Louis University, St. Louis, Missouri, 63104, USA.
Biochem Biophys Res Commun. 1999 Jul 5;260(2):405-9. doi: 10.1006/bbrc.1999.0921.
MBP-1, a c-myc promoter binding protein, is a mammalian transcription factor with intriguing properties including transcriptional repression of cellular genes. Recently, we have identified and characterized two different repressor domains of MBP-1. In this report, we have demonstrated that MBP-1 physically associates with histone deacetylase (HDAC), thus promoting formation of neucleosomes that inhibit transcription. Trichostatin A, an inhibitor of histone deacetylase, significantly reduces MBP-1-mediated transcriptional repression. However, MBP-1-mediated repression on c-myc promoter is resistant to histone deacetylase activity. Our results suggest that MBP-1 represses transcription by recruiting histone deacetylase as one of the mechanisms, whereas the other mechanism is resistant to HDAC activity and probably related to direct binding of promoter sequences or interaction through yet unidentified factor.
MBP-1是一种与c-myc启动子结合的蛋白,是一种具有有趣特性的哺乳动物转录因子,包括对细胞基因的转录抑制。最近,我们鉴定并表征了MBP-1的两个不同的抑制域。在本报告中,我们证明MBP-1与组蛋白脱乙酰基酶(HDAC)发生物理结合,从而促进抑制转录的核小体形成。曲古抑菌素A是一种组蛋白脱乙酰基酶抑制剂,可显著降低MBP-1介导的转录抑制。然而,MBP-1对c-myc启动子的抑制作用对组蛋白脱乙酰基酶活性具有抗性。我们的结果表明,MBP-1通过招募组蛋白脱乙酰基酶作为其中一种机制来抑制转录,而另一种机制对HDAC活性具有抗性,可能与启动子序列的直接结合或通过尚未确定的因子的相互作用有关。