Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Immunol Rev. 2021 Mar;300(1):167-180. doi: 10.1111/imr.12942. Epub 2021 Jan 15.
An extraordinary degree of condensation is required to fit the eukaryotic genome inside the nucleus. This compaction is attained by first coiling the DNA around structures called nucleosomes. Mammalian genomes are further folded into sophisticated three-dimensional (3D) configurations, enabling the genetic code to dictate a diverse range of cell fates. Recent advances in molecular and computational technologies have enabled the query of higher-order chromatin architecture at an unprecedented resolution and scale. In T lymphocytes, similar to other developmental programs, the hierarchical genome organization is shaped by a highly coordinated division of labor among different classes of sequence-specific transcription factors. In this review, we will summarize the general principles of 1D and 3D genome organization, introduce the common experimental and computational techniques to measure the multilayer chromatin organization, and discuss the pervasive role of transcription factors on chromatin organization in T lymphocytes.
真核生物基因组要装入细胞核内，需要极高程度的压缩。这种压缩首先通过将 DNA 卷曲成称为核小体的结构来实现。哺乳动物基因组进一步折叠成复杂的三维（3D）结构，使遗传密码能够决定多种细胞命运。分子和计算技术的最新进展使人们能够以前所未有的分辨率和规模查询更高阶的染色质结构。在 T 淋巴细胞中，与其他发育程序类似，分层基因组组织是通过不同类别的序列特异性转录因子之间高度协调的分工来塑造的。在这篇综述中，我们将总结 1D 和 3D 基因组组织的一般原则，介绍测量多层染色质组织的常用实验和计算技术，并讨论转录因子在 T 淋巴细胞中对染色质组织的普遍作用。
