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Insight into the machinery that oils chromatin dynamics

机译：深入了解为染色质动力学提供动力的机械

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The packaging of genetic information in form of chromatin within the nucleus provides cells with the ability to store and protect massive amounts of information within a compact space. Storing information within chromatin allows selective access to specific DNA sequences by regulating the various levels of chromatin structure from nucleosomes, to chromatin fibers, loops and topological associating domains (TADs) using mechanisms that are being progressively unravelled. However, a relatively unexplored aspect is the energetic cost of changing the chromatin configuration to gain access to DNA information. Among the enzymes responsible for regulating chromatin access are the ATP-dependent chromatin remodellers that act on nucleosomes and use the energy of ATP hydrolysis to make chromatin DNA more accessible. It is assumed that the ATP used by these enzymes is provided by the mitochondria or by cytoplasmic glycolysis. We hypothesize that though this may be the case for cells in steady state, when gene expression has to be globally reprogramed in response to externals signals or stress conditions, the cell directs energy production to the cell nucleus, where rapid chromatin reorganization is needed for cell survival. We discovered that in response to hormones a nuclear ATP synthesis mechanism is activated that utilizing ADP-ribose and pyrophosphate as substrates.~(1) Wright RH, Lioutas A, Le Dily F, Soronellas D, Pohl A, Bonet J, Nacht AS, Samino S, Font-Mateu J, Vicent GP, et?al. ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling. Science 2016; 352:1221-5; PMID:27257257; http://dx.doi.org/10.1126/science.aad9335[Crossref], [PubMed], [Web of Science ®]?[Google Scholar] This extra view aims to put this process within its historical context, to describe the enzymatic steps in detail, to propose a possible structure of the ATP synthesising enzyme, and to shed light on how this may link to other reactions within the cell providing a perspective for future lines of investigation.
机译：将遗传信息以染色质的形式包装在细胞核内，使细胞能够在紧凑的空间内存储和保护大量信息。在染色质中存储信息，可以通过逐步阐明机制来调节从核小体到染色质纤维，环和拓扑关联域（TAD）的各种染色质结构水平，从而选择性地访问特定的DNA序列。然而，一个相对未开发的方面是改变染色质构型以获得对DNA信息的访问的能源成本。在负责调节染色质进入的酶中，有ATP依赖的染色质重塑剂，其作用于核小体，并利用ATP水解的能量使染色质DNA更易接近。假定这些酶使用的ATP是由线粒体或细胞质糖酵解提供的。我们假设虽然稳态细胞可能会发生这种情况，但是当必须响应外部信号或压力条件对基因表达进行全局重新编程时，细胞会将能量产生导向细胞核，因此细胞需要快速染色质重组生存。我们发现，对激素的反应是利用ADP-核糖和焦磷酸盐作为底物来激活核ATP合成机制。〜（1）Wright RH，Lioutas A，Le Dily F，Soronellas D，Pohl A，Bonet J，Nacht AS， Samino S，Font-Mateu J，Vicent GP等。染色质重塑需要NUDIX5合成ADP核糖衍生的核ATP。科学2016; 352：1221-5; PMID：27257257; http://dx.doi.org/10.1126/science.aad9335[Crossref]、[PubMed]、[Web of Science®]？[Google Scholar]这种额外的观点旨在将这一过程置于其历史背景下，以描述酶的详细步骤，以提出ATP合成酶的可能结构，并阐明该酶如何与细胞内的其他反应联系起来，为将来的研究方向提供了一个视角。

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