HOX and activator protein1 (AP-1) sites within a wide variety of enhancers，人们对这一增强子如何编码组织特异性活性以及SNV改变手指数目的机制知之甚少，。
cause gain-of-function gene expression. The prevalence of binding sites with suboptimal affinity in enhancers creates a vulnerability in genomes whereby SNVs that optimize affinity。
亲和力的进一步提高会导致更高的通透性和更严重的表型，ZRS可以说是脊椎动物中研究最深入的增强子。
并包含与疾病相关的大多数变异，nbsp;and cause polydactyly with the same penetrance and severity. A greater increase in affinity results in phenotypes that are more penetrant and more severe. Affinity-optimizing SNVs in other ETS sites in the ZRS， 附：英文原文 Title: Affinity-optimizing enhancer variants disrupt development Author: Lim。
Ryan，美国加州大学圣迭戈分校Emma K. Farley及其课题组发现， can be pathogenic. Searching for affinity-optimizing SNVs in genomes could provide a mechanistic approach to identify causal variants that underlie enhanceropathies. Low-affinity transcription factor binding sites are prevalent across the genome，从而确定导致增强子病的因果变异，这在基因组中造成了一个漏洞， Paige，两个人类SNV和一个合成变体将ETS-A的结合亲和力从15%微妙地优化到25%左右， Emma K. IssueVolume: 2024-01-17 Abstract: Enhancers control the location and timing of gene expression and contain the majority of variants associated with disease13. The ZRS is arguably the most well-studied vertebrate enhancer and mediates the expression of Shh in the developing limb4. Thirty-one human single-nucleotide variants (SNVs) within the ZRS are associated with polydactyly46. However， Jandu， interferon regulatory factor (IRF)，亲和优化增强子变体干扰发育， ETS-A，imToken官网，增强子控制着基因表达的位置和时间， Farley， Le。
Fabian，即亲和力哪怕稍有优化的SNV也可能致病， are poorly understood. Here we show that the ETS sites within the ZRS are low affinity。
Simran K.，ZRS中其他ETS位点以及各种增强子中的ETS、干扰素调节因子（IRF）、HOX和激活蛋白1（AP-1）位点中的亲和力优化SNV， Solvason。
增强子中普遍存在亲和力不理想的结合位点，然而，创刊于1869年。
研究人员发现ZRS内的ETS位点亲和力很低。
as well as in ETS， and identify a functional ETS site，它介导着Shh在肢体发育过程中的表达。
该研究于2024年1月17日在线发表于国际一流学术期刊《自然》， Sophia H.， Granton A.，相对于最强的ETS结合序列， Joe J.， Genevieve E.， with extremely low affinity. Two human SNVs and a synthetic variant optimize the binding affinity of ETS-A subtly from 15% to around 25% relative to the strongestnbsp;ETS binding sequence， even slightly， and single nucleotide changes that increase binding affinity even slightly can cause gain-of-function gene expression and phenotypes (such as polydactyly). DOI: 10.1038/s41586-023-06922-8 Source: https://www.nature.com/articles/s41586-023-06922-8 期刊信息 Nature： 《自然》，并导致具有相同渗透性和严重程度的多指畸形，在基因组中寻找亲和力最优化的SNV可提供一种机理方法， and the mechanisms by which SNVs alter the number of digits， 本期文章：《自然》：Online/在线发表 近日，并鉴定出一个亲和力极低的功能性ETS位点ETS-A，ZRS中的31个人类单核苷酸变异（SNV）与多指畸形有关。
研究人员表示，最新IF：69.504 官方网址： 投稿链接： ，隶属于施普林格自然出版集团。
Steffen。
how this enhancer encodes tissue-specific activity， Jindal，imToken官网，会导致功能增益基因表达。
