Dong Jinhong, Sathyan Kizhakke Mattada, Scott Thomas G, Mukherjee Rudradeep, Guertin Michael J
Center for Cell Analysis and Modeling, University of Connecticut, 400 Farmington Ave, Farmington, Connecticut 06030, USA.
Department of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Ave, Charlottesville, Virginia 22903, USA.
Nucleic Acids Res. 2025 Jan 11;53(2). doi: 10.1093/nar/gkae1182.
Transcription factors bind to sequence motifs and act as activators or repressors. Transcription factors interface with a constellation of accessory cofactors to regulate distinct mechanistic steps to regulate transcription. We rapidly degraded the essential and pervasively expressed transcription factor ZNF143 to determine its function in the transcription cycle. ZNF143 facilitates RNA polymerase initiation and activates gene expression. ZNF143 binds the promoter of nearly all its activated target genes. ZNF143 also binds near the site of genic transcription initiation to directly repress a subset of genes. Although ZNF143 stimulates initiation at ZNF143-repressed genes (i.e. those that increase transcription upon ZNF143 depletion), the molecular context of binding leads to cis repression. ZNF143 competes with other more efficient activators for promoter access, physically occludes transcription initiation sites and promoter-proximal sequence elements, and acts as a molecular roadblock to RNA polymerases during early elongation. The term context specific is often invoked to describe transcription factors that have both activation and repression functions. We define the context and molecular mechanisms of ZNF143-mediated cis activation and repression.
转录因子与序列基序结合，充当激活剂或抑制剂。转录因子与一系列辅助共因子相互作用，以调节不同的机制步骤来调控转录。我们快速降解了基本且广泛表达的转录因子ZNF143，以确定其在转录周期中的功能。ZNF143促进RNA聚合酶起始并激活基因表达。ZNF143结合几乎所有其激活的靶基因的启动子。ZNF143也结合在基因转录起始位点附近，直接抑制一部分基因。尽管ZNF143在ZNF143抑制的基因（即那些在ZNF143缺失时转录增加的基因）上刺激起始，但结合的分子背景导致顺式抑制。ZNF143与其他更有效的激活剂竞争启动子结合，物理上封闭转录起始位点和启动子近端序列元件，并在早期延伸过程中对RNA聚合酶起分子阻碍作用。“上下文特异性”一词常被用来描述具有激活和抑制功能的转录因子。我们定义了ZNF143介导的顺式激活和抑制的背景及分子机制。
