Barutcu A Rasim, Lian Jane B, Stein Janet L, Stein Gary S, Imbalzano Anthony N
a Department of Cell and Developmental Biology , University of Massachusetts Medical School , Worcester , MA , USA.
b Department of Biochemistry , University of Vermont College of Medicine , Burlington , VT , USA.
Nucleus. 2017 Mar 4;8(2):150-155. doi: 10.1080/19491034.2016.1276145. Epub 2017 Jan 6.
The eukaryotic genome is partitioned into topologically associating domains (TADs). Despite recent advances characterizing TADs and TAD boundaries, the organization of these structures is an important dimension of genome architecture and function that is not well understood. Recently, we demonstrated that knockdown of BRG1, an ATPase driving the chromatin remodeling activity of mammalian SWI/SNF enzymes, globally alters long-range genomic interactions and results in a reduction of TAD boundary strength. We provided evidence suggesting that this effect may be due to BRG1 affecting nucleosome occupancy around CTCF sites present at TAD boundaries. In this review, we elaborate on our findings and speculate that BRG1 may contribute to the regulation of the structural and functional properties of chromatin at TAD boundaries by affecting the function or the recruitment of CTCF and DNA topoisomerase complexes.
真核生物基因组被划分为拓扑相关结构域（TADs）。尽管最近在表征TADs和TAD边界方面取得了进展，但这些结构的组织是基因组结构和功能的一个重要方面，目前尚未得到很好的理解。最近，我们证明，敲低BRG1（一种驱动哺乳动物SWI/SNF酶染色质重塑活性的ATP酶）会全局改变远程基因组相互作用，并导致TAD边界强度降低。我们提供的证据表明，这种效应可能是由于BRG1影响了TAD边界处CTCF位点周围的核小体占有率。在这篇综述中，我们详细阐述了我们的发现，并推测BRG1可能通过影响CTCF和DNA拓扑异构酶复合物的功能或募集，对TAD边界处染色质的结构和功能特性的调节做出贡献。
