Genetics and Molecular Biology Graduate Program, Emory University, Atlanta, GA 30322, USA.
Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA 30322, USA.
Genetics. 2024 Jul 8;227(3). doi: 10.1093/genetics/iyae060.
Despite binding similar cis elements in multiple locations, a single transcription factor (TF) often performs context-dependent functions at different loci. How factors integrate cis sequence and genomic context is still poorly understood and has implications for off-target effects in genetic engineering. The Drosophila context-dependent TF chromatin-linked adaptor for male-specific lethal proteins (CLAMP) targets similar GA-rich cis elements on the X-chromosome and at the histone gene locus but recruits very different, locus-specific factors. We discover that CLAMP leverages information from both cis element and local sequence to perform context-specific functions. Our observations imply the importance of other cues, including protein-protein interactions and the presence of additional cofactors.
尽管单一转录因子（TF）在多个位置结合相似的顺式元件，但它通常在不同位置执行依赖于上下文的功能。TF 如何整合顺式序列和基因组上下文仍然知之甚少，这对遗传工程中的脱靶效应有影响。果蝇中与雄性致死蛋白（CLAMP）相关的染色质连接顺式元件适应性转录因子（chromatin-linked adaptor for male-specific lethal proteins，CLAMP）靶向 X 染色体和组蛋白基因座上相似的 GA 富集顺式元件，但招募的是非常不同的、具有特定位置的因子。我们发现 CLAMP 利用顺式元件和局部序列的信息来执行特定于上下文的功能。我们的观察结果表明，其他线索（包括蛋白质-蛋白质相互作用和额外辅助因子的存在）的重要性。
