生物技术进展 ›› 2022, Vol. 12 ›› Issue (1): 27-35.DOI: 10.19586/j.2095-2341.2021.0132
王婉洁(), 陈南珠, 郝海生, 赵学明, 朱化彬, 杜卫华(
)
收稿日期:
2021-07-13
接受日期:
2021-10-08
出版日期:
2022-01-25
发布日期:
2022-01-26
通讯作者:
杜卫华
作者简介:
王婉洁E-mail:wangwanjie101@163.com;
基金资助:
Wanjie WANG(), Nanzhu CHEN, Haisheng HAO, Xueming ZHAO, Huabin ZHU, Weihua DU(
)
Received:
2021-07-13
Accepted:
2021-10-08
Online:
2022-01-25
Published:
2022-01-26
Contact:
Weihua DU
摘要:
表观遗传修饰通过改变染色质空间构象和基因表达调控胚胎发育、细胞分化、器官发生和癌症形成,其调控形式包括组蛋白甲基化、组蛋白乙酰化、DNA甲基化、基因印迹和X染色体失活等。缺失的、小的、同源异形2(absent, small, homologous 2,ASH2)是组蛋白赖氨酸甲基转移酶复合物的核心成分,其属于三胸腔结构蛋白家族;在哺乳动物中ASH2可特异性甲基化H3K4,激活基因转录。在介绍组蛋白甲基化和三胸腔结构蛋白的基础上,综述了ASH2甲基酶对基因转录、HOX基因表达、癌症发生发展和细胞分化的调控功能,以期为其在动物繁育和人类疾病治疗中的应用提供思路。
中图分类号:
王婉洁, 陈南珠, 郝海生, 赵学明, 朱化彬, 杜卫华. 组蛋白甲基转移酶ASH2的研究进展[J]. 生物技术进展, 2022, 12(1): 27-35.
Wanjie WANG, Nanzhu CHEN, Haisheng HAO, Xueming ZHAO, Huabin ZHU, Weihua DU. Research Progress of Histone Methyltransferases ASH2[J]. Current Biotechnology, 2022, 12(1): 27-35.
图1 TrxG和PcG相互拮抗的动态平衡[20]A:PcG和TrxG复合物的动态平衡影响多种生物学过程;B:PcG和TrxG复合物通过多种反应元件的调节发挥拮抗作用
Fig.1 Dynamic equilibrium of mutual antagonism between TrxG and PcG[20]
亚基 | 复合物 | 哺乳动物同源物 | 分子功能 |
---|---|---|---|
PC | PRC1 | CBX2、CBX4、CBX6、CBX7、CBX8 | 通过染色质结构域与H2K27me3结合 |
PSC | PRC1 | BMI1(PCGF4)、MEL18(PCGF2) | 含锌指结构域蛋白,与DNA和致密染色质结合 |
PH | PRC1 | PHC1(EDR1)、PHC2(EDR2)、PHC3(EDR3) | 具有锌指结构域,促进蛋白自聚集 |
SCE(DRING1) | PRC1 | RING1A、RING1B | E3泛素连接酶,单双酯化H2AK118(哺乳动物中的K119) |
E(Z) | PRC2 | EZH1、EZH2 | 通过SET结构域甲基化H3K27 |
SU(Z)12 | PRC2 | SUZ12 | 通过VEFS‑box结构域增强E(Z)活性 |
ESC | PRC2 | EED | 通过WD重复序列促进蛋白间相互作用,通过结合H3K27me3增强抑制作用 |
P55(NURF55、CAF1) | PRC2 | RBAP46、RBAP48 | 与SU(Z)12和组蛋白相互作用 |
PHO | PHORC | YY1 | 通过锌指结构特异性地结合DNA序列 |
SFMBT | PHORC | — | 结合甲基化的H3和H4赖氨酸 |
表1 PcG复合物成分[26]
Table 1 Composition of PcG complex[26]
亚基 | 复合物 | 哺乳动物同源物 | 分子功能 |
---|---|---|---|
PC | PRC1 | CBX2、CBX4、CBX6、CBX7、CBX8 | 通过染色质结构域与H2K27me3结合 |
PSC | PRC1 | BMI1(PCGF4)、MEL18(PCGF2) | 含锌指结构域蛋白,与DNA和致密染色质结合 |
PH | PRC1 | PHC1(EDR1)、PHC2(EDR2)、PHC3(EDR3) | 具有锌指结构域,促进蛋白自聚集 |
SCE(DRING1) | PRC1 | RING1A、RING1B | E3泛素连接酶,单双酯化H2AK118(哺乳动物中的K119) |
E(Z) | PRC2 | EZH1、EZH2 | 通过SET结构域甲基化H3K27 |
SU(Z)12 | PRC2 | SUZ12 | 通过VEFS‑box结构域增强E(Z)活性 |
ESC | PRC2 | EED | 通过WD重复序列促进蛋白间相互作用,通过结合H3K27me3增强抑制作用 |
P55(NURF55、CAF1) | PRC2 | RBAP46、RBAP48 | 与SU(Z)12和组蛋白相互作用 |
PHO | PHORC | YY1 | 通过锌指结构特异性地结合DNA序列 |
SFMBT | PHORC | — | 结合甲基化的H3和H4赖氨酸 |
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