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条形码筛选技术揭示了表观遗传调控因子在组蛋白周转中的作用，该技术发现 NuB4/HAT-B 组蛋白乙酰转移酶复合物在组蛋白周转中发挥作用。

A barcode screen for epigenetic regulators reveals a role for the NuB4/HAT-B histone acetyltransferase complex in histone turnover.

机构信息

Department of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands.

出版信息

PLoS Genet. 2011 Oct;7(10):e1002284. doi: 10.1371/journal.pgen.1002284. Epub 2011 Oct 6.

DOI:10.1371/journal.pgen.1002284
PMID:21998594
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3188528/
Abstract

Dynamic modification of histone proteins plays a key role in regulating gene expression. However, histones themselves can also be dynamic, which potentially affects the stability of histone modifications. To determine the molecular mechanisms of histone turnover, we developed a parallel screening method for epigenetic regulators by analyzing chromatin states on DNA barcodes. Histone turnover was quantified by employing a genetic pulse-chase technique called RITE, which was combined with chromatin immunoprecipitation and high-throughput sequencing. In this screen, the NuB4/HAT-B complex, containing the conserved type B histone acetyltransferase Hat1, was found to promote histone turnover. Unexpectedly, the three members of this complex could be functionally separated from each other as well as from the known interacting factor and histone chaperone Asf1. Thus, systematic and direct interrogation of chromatin structure on DNA barcodes can lead to the discovery of genes and pathways involved in chromatin modification and dynamics.

摘要

组蛋白蛋白的动态修饰在调节基因表达中起着关键作用。然而，组蛋白本身也可以是动态的，这可能会影响组蛋白修饰的稳定性。为了确定组蛋白周转的分子机制，我们通过分析 DNA 条码上的染色质状态开发了一种用于表观遗传调节剂的平行筛选方法。通过称为 RITE 的遗传脉冲追踪技术来定量组蛋白周转，该技术与染色质免疫沉淀和高通量测序相结合。在该筛选中，发现包含保守的 B 型组蛋白乙酰转移酶 Hat1 的 NuB4/HAT-B 复合物可促进组蛋白周转。出乎意料的是，该复合物的三个成员可以彼此以及已知的相互作用因子和组蛋白伴侣 Asf1 功能分离。因此，对 DNA 条码上的染色质结构进行系统和直接的询问可以发现参与染色质修饰和动力学的基因和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/78e998594d7a/pgen.1002284.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/e52ef2032fe9/pgen.1002284.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/3f1d5a75bba2/pgen.1002284.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/4131c8c0ccc1/pgen.1002284.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/9576c8ef2248/pgen.1002284.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/bbf71120bd98/pgen.1002284.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/406c9393bf0f/pgen.1002284.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/78e998594d7a/pgen.1002284.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/e52ef2032fe9/pgen.1002284.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/3f1d5a75bba2/pgen.1002284.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/4131c8c0ccc1/pgen.1002284.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/9576c8ef2248/pgen.1002284.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/bbf71120bd98/pgen.1002284.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/406c9393bf0f/pgen.1002284.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8c/3188528/78e998594d7a/pgen.1002284.g007.jpg

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