Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Annu Rev Genet. 2012;46:43-68. doi: 10.1146/annurev-genet-110711-155437. Epub 2012 Aug 28.
Regulation of gene expression in eukaryotes is an extremely complex process. In this review, we break down several critical steps, emphasizing new data and techniques that have expanded current gene regulatory models. We begin at the level of DNA sequence where cis-regulatory modules (CRMs) provide important regulatory information in the form of transcription factor (TF) binding sites. In this respect, CRMs function as instructional platforms for the assembly of gene regulatory complexes. We discuss multiple mechanisms controlling complex assembly, including cooperative DNA binding, combinatorial codes, and CRM architecture. The second section of this review places CRM assembly in the context of nucleosomes and condensed chromatin. We discuss how DNA accessibility and histone modifications contribute to TF function. Lastly, new advances in chromosomal mapping techniques have provided increased understanding of intra- and interchromosomal interactions. We discuss how these topological maps influence gene regulatory models.
真核生物中的基因表达调控是一个极其复杂的过程。在这篇综述中，我们分解了几个关键步骤，强调了新的数据和技术，这些数据和技术扩展了当前的基因调控模型。我们从 DNA 序列水平开始，顺式调控模块（CRMs）以转录因子（TF）结合位点的形式提供重要的调控信息。在这方面，CRMs 作为基因调控复合物组装的指令平台发挥作用。我们讨论了多种控制复杂组装的机制，包括协同 DNA 结合、组合密码和 CRM 结构。本综述的第二部分将 CRM 组装置于核小体和浓缩染色质的背景下进行讨论。我们讨论了 DNA 可及性和组蛋白修饰如何影响 TF 的功能。最后，染色体作图技术的新进展提供了对染色体内和染色体间相互作用的更深入理解。我们讨论了这些拓扑图谱如何影响基因调控模型。
