Non-canonical functions of enhancers: regulation of RNA polymerase III transcription, DNA replication, and V(D)J recombination

IF 13.6 2区 生物学 Q1 GENETICS & HEREDITY Trends in Genetics Pub Date : 2024-04-19 DOI:10.1016/j.tig.2024.04.001
Kevin Struhl
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Abstract

Enhancers are the key regulators of other DNA-based processes by virtue of their unique ability to generate nucleosome-depleted regions in a highly regulated manner. Enhancers regulate cell-type-specific transcription of tRNA genes by RNA polymerase III (Pol III). They are also responsible for the binding of the origin replication complex (ORC) to DNA replication origins, thereby regulating origin utilization, replication timing, and replication-dependent chromosome breaks. Additionally, enhancers regulate V(D)J recombination by increasing access of the recombination-activating gene (RAG) recombinase to target sites and by generating non-coding enhancer RNAs and localized regions of trimethylated histone H3-K4 recognized by the RAG2 PHD domain. Thus, enhancers represent the first step in decoding the genome, and hence they regulate biological processes that, unlike RNA polymerase II (Pol II) transcription, do not have dedicated regulatory proteins.

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增强子的非规范功能:调节 RNA 聚合酶 III 转录、DNA 复制和 V(D)J 重组
增强子具有以高度受控的方式生成核糖体缺失区的独特能力,是其他 DNA 过程的关键调控因子。增强子通过 RNA 聚合酶 III(Pol III)调节细胞类型特异性的 tRNA 基因转录。增强子还负责将起源复制复合体(ORC)与 DNA 复制起源结合,从而调节起源的利用、复制时间和复制依赖性染色体断裂。此外,增强子通过增加重组激活基因(RAG)重组酶进入目标位点的机会,以及通过产生非编码增强子 RNA 和 RAG2 PHD 结构域识别的三甲基化组蛋白 H3-K4 的局部区域,调节 V(D)J 重组。因此,增强子代表了基因组解码的第一步,因此它们调控的生物过程与 RNA 聚合酶 II(Pol II)转录不同,没有专门的调控蛋白。
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来源期刊
Trends in Genetics
Trends in Genetics 生物-遗传学
CiteScore
20.90
自引率
0.90%
发文量
160
审稿时长
6-12 weeks
期刊介绍: Launched in 1985, Trends in Genetics swiftly established itself as a "must-read" for geneticists, offering concise, accessible articles covering a spectrum of topics from developmental biology to evolution. This reputation endures, making TiG a cherished resource in the genetic research community. While evolving with the field, the journal now embraces new areas like genomics, epigenetics, and computational genetics, alongside its continued coverage of traditional subjects such as transcriptional regulation, population genetics, and chromosome biology. Despite expanding its scope, the core objective of TiG remains steadfast: to furnish researchers and students with high-quality, innovative reviews, commentaries, and discussions, fostering an appreciation for advances in genetic research. Each issue of TiG presents lively and up-to-date Reviews and Opinions, alongside shorter articles like Science & Society and Spotlight pieces. Invited from leading researchers, Reviews objectively chronicle recent developments, Opinions provide a forum for debate and hypothesis, and shorter articles explore the intersection of genetics with science and policy, as well as emerging ideas in the field. All articles undergo rigorous peer-review.
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