超级强化子

在遗传学，超级强化子（Super-enhancer）是哺乳类基因体中包含多个强化子的区域，可以结合许多转录因子来启动决定细胞分化结果之基因的转录。^[1][2][3]由于超级强化子经常出现于控制、定义细胞身份基因的附近，因此它们也可被用来快速定位基因组中调控细胞身份的关键位点。^[3][4]

超级强化子会与许多与转录调控相关的蛋白结合，并常用于调控高表现量的基因表现^[1][5][6][7]与超级强化子相关的基因表现会特别对扰动敏感，可能控制细胞状态的转换，这也导致由超级强化子调控的基因常对影响转录的小分子较为敏感。^{[1][5][6][8][9]}

历史

有关强化子对转录调控的研究始于1980年代。^{[10][11][12][13][14]} 不久后发现了一些大型或多单元的转录调控区域，包含基因座控制区、成簇的开放调控元件与转录起始的平台等。^{[15][16][17][18]}近期的研究结果表明，这些不同类别的调控单元可能都属于超级强化子。^[19]

2013年，两组研究团队分别在基因组中对决定细胞分化种类重要的位点附近发现了大型强化子，其中理查德·杨（英语：Richard A. Young）的团队发现了超级强化子，法兰西斯·柯林斯的团队则发现了延伸强化子（stretch enhancers）。^[20][21]超级强化子及延伸强化子皆为成簇的强化子，控制了细胞中特定的基因表现，可能是极为相似的元件。^[21][22]

根据目前定义，“超级强化子”一词由美国遗传学家理查德·杨的团队定义，用来描述在小鼠的胚胎干细胞中发现^[20]、长度较长、且能控制影响干细胞分化结果之基因（包括Oct-4、Sox2、Nanog、KLF4 以及 Esrrb等）表现的特定元件。干扰调控这些基因的超级强化子会严重影响这些基因的表现。^[22]超级强化子已经在一些小鼠与人类组织的基因组中，负责控制细胞分化结果之基因附近被发现。^{[21][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]}

功能

相关疾病

侦测方式

超级强化子的侦测方式，大多是以染色质免疫沉淀-测序侦测主要转录因子、中介体（英语：Mediator (coactivator)）与BRD4蛋白（英语：BRD4）等共同因子（英语：Transcription coregulator）或H3K27ac核小体（英语：H3K27ac）在基因组中的结合位点，其中以H3K27ac核小体最为常用。^{[1][3][6][41][42][43]}理察·杨的团队开发了一个称为“ROSE”（Rank Ordering of Super-Enhancers）的程式，可用于从染色质免疫沉淀定序的结果中侦测超级强化子，这个程式可依据超级强化子中某些标记的含量比一般强化子更多的特性，判定数个已知的强化子是否组成超级强化子，而用以判定的间距标准可依不同情况调整。^[1]

参考资料

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