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首页> 外文期刊>Pigment cell research >T-box factors: targeting to chromatin and interaction with the histone H3N-terminal tail
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T-box factors: targeting to chromatin and interaction with the histone H3N-terminal tail

机译：T-box因子：靶向染色质并与组蛋白H3N末端尾巴相互作用

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T-box transcription factors play a crucial role in development where they are implicated in patterning and cell fate decisions. Tbx2 and Tbx3 have also been implicated in several cancers including melanoma, and can act as antisenescence factors through their ability to repress p19(ARF) and p21(ClP1) expression. Although several target genes for T-box factors have been identified, it is unknown whether this family of proteins can bind chromatin, a property that would facilitate the epigenetic reprogramming that occurs in both development and cancer progression. Here, we show that Tbx2 has the potential to recognize mitotic chromatin in a DNA-dependent fashion, can interact specifically with the histone H3 N-terminal tail, a property shared with Tbx4, Tbx5 and Tbx6, and can also recognize nucleosomal DNA, with binding to nucleosomes being antagonized by the presence of the histone tails. Strikingly, in vivo Tbx2 co-localization with pericentric heterochromatin appears to be regulated and ectopic expression of Tbx2 leads to severe mitotic defects. Taken together our results suggest that Tbx2, and most likely other members of the T-box family, are able to target chromatin and may indicate a role for the T-box factors in epigenetic reprogramming events.
机译：T-box转录因子在发育中起着至关重要的作用，其中涉及到模式和细胞命运的决定。 Tbx2和Tbx3也与包括黑色素瘤在内的多种癌症有关，并通过其抑制p19（ARF）和p21（ClP1）表达的能力而发挥抗衰老作用。尽管已经确定了T-box因子的几个靶基因，但尚不清楚该蛋白家族是否可以结合染色质，这种特性将促进在发育和癌症进展中发生的表观遗传重编程。在这里，我们显示Tbx2具有以DNA依赖性方式识别有丝分裂染色质的潜能，可以与组蛋白H3 N末端尾巴特异性相互作用，这是与Tbx4，Tbx5和Tbx6共享的特性，并且还可以识别核小体DNA与组蛋白尾巴的存在拮抗的核小体结合。引人注目的是，体内Tbx2与周围中心异染色质的共定位似乎受到调节，Tbx2的异位表达导致严重的有丝分裂缺陷。总之，我们的结果表明，Tbx2和T-box家族的其他成员很可能能够靶向染色质，并可能表明T-box因子在表观遗传重编程事件中的作用。

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