Chemical Biology Program, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
J Am Chem Soc. 2017 Jul 12;139(27):9090-9096. doi: 10.1021/jacs.7b03430. Epub 2017 Jun 27.
Chromosomes present one of most challenging of all substrates for biochemical study. This is because genomic DNA is physically associated with an astonishing collection of nuclear factors, which serve to not only store the nucleic acid in a stable form, but also grant access to the information it encodes when needed. Understanding this complex molecular choreography is central to the field of epigenetics. One of the great challenges in this area is to move beyond correlative type information, which is now in abundant supply, to the point where we can truly connect the dots at the molecular level. Establishing such causal relationships requires precise manipulation of the covalent structure of chromatin. Tools for this purpose are currently in short supply, creating an opportunity that, as we will argue in this Perspective, is well suited to the sensibilities of the chemist.
染色体是生物化学研究中最具挑战性的底物之一。这是因为基因组 DNA 与令人惊讶的核因子集合物理相关，这些核因子不仅有助于以稳定的形式储存核酸，还能在需要时赋予其访问所编码信息的权限。理解这种复杂的分子舞蹈是表观遗传学领域的核心。该领域的一大挑战是超越目前大量存在的相关信息，达到我们能够在分子水平真正关联各个点的程度。建立这种因果关系需要对染色质的共价结构进行精确操作。目前，实现这一目的的工具非常短缺，这为化学家提供了一个机会，正如我们将在这篇观点文章中论证的那样，这种机会非常适合化学家。
