Cell type-specific gene expression relies on transcription factors (TFs) binding DNA sequence motifs embedded in chromatin. Understanding how motifs are accessed in chromatin is crucial to comprehend differential transcriptional responses and the phenotypic impact of sequence variation. Chromatin obstacles to TF binding range from DNA methylation to restriction of DNA access by nucleosomes depending on their position, composition and modification. In vivo and in vitro approaches now enable the study of TF binding in chromatin at unprecedented resolution. Emerging insights suggest that TFs vary in their ability to navigate chromatin states. However, it remains challenging to link binding and transcriptional outcomes to molecular characteristics of TFs or the local chromatin substrate. Here, we discuss our current understanding of how TFs access DNA in chromatin and novel techniques and directions towards a better understanding of this critical step in genome regulation.

细胞类型特异性基因表达依赖于转录因子 (TF) 结合嵌入染色质中的 DNA 序列基序。了解染色质中基序的访问方式对于理解差异转录反应和序列变异的表型影响至关重要。染色质对 TF 结合的障碍范围从 DNA 甲基化到核小体对 DNA 访问的限制，具体取决于它们的位置、组成和修饰。体内和体外方法现在能够以前所未有的分辨率研究染色质中的 TF 结合。新出现的见解表明，TF 的导航染色质状态的能力各不相同。然而，将结合和转录结果与转录因子或局部染色质底物的分子特征联系起来仍然具有挑战性。这里，