Chemical Biology Approaches to Identify and Profile Interactors of Chromatin Modifications.

Chemical Biology Approaches to Identify and Profile Interactors of Chromatin Modifications.
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DOI:
10.1021/acschembio.1c00794
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发表时间:
2022-03
影响因子:
4
通讯作者:
Garrison A Nickel;Katharine L. Diehl
Garrison A Nickel;Katharine L. Diehl
中科院分区:
生物学2区
文献类型:
--
作者:
Garrison A Nickel;Katharine L. Diehl

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在真核生物中,DNA 与组蛋白一起包装在称为染色质的复合物中。染色质的 DNA 和组蛋白成分都可以通过多种方式进行化学修饰,从而形成通常被称为“表观遗传密码”的复杂景观。这些修饰被效应蛋白识别,从而重塑染色质并调节底层 DNA 的转录、翻译和修复。在这篇综述中,我们研究了表征与这些组蛋白和 DNA 修饰相互作用的蛋白质的方法的发展。 “标记优先”方法利用化学、肽、核小体或寡核苷酸探针来发现特定修饰的相互作用物。 “读者优先”方法采用肽、核小体或寡核苷酸阵列来分析相互作用物的结合偏好。这些互补策略极大地增强了我们对染色质修饰如何影响基因组调控变化的理解,使我们更接近破译这种复杂的语言。
In eukaryotes, DNA is packaged with histone proteins in a complex known as chromatin. Both the DNA and histone components of chromatin can be chemically modified in a wide variety of ways, resulting in a complex landscape often referred to as the "epigenetic code". These modifications are recognized by effector proteins that remodel chromatin and modulate transcription, translation, and repair of the underlying DNA. In this Review, we examine the development of methods for characterizing proteins that interact with these histone and DNA modifications. "Mark first" approaches utilize chemical, peptide, nucleosome, or oligonucleotide probes to discover interactors of a specific modification. "Reader first" approaches employ arrays of peptides, nucleosomes, or oligonucleotides to profile the binding preferences of interactors. These complementary strategies have greatly enhanced our understanding of how chromatin modifications effect changes in genomic regulation, bringing us ever closer to deciphering this complex language.