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人类 KRAB 锌指蛋白的遗传特征和基因组靶标。

Genetic features and genomic targets of human KRAB-zinc finger proteins.

机构信息

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

Precision Medicine Unit, Lausanne University Hospital (CHUV) and University of Lausanne, 1010 Lausanne, Switzerland.

出版信息

Genome Res. 2023 Aug;33(8):1409-1423. doi: 10.1101/gr.277722.123. Epub 2023 Sep 20.

Abstract

Krüppel-associated box (KRAB) domain-containing zinc finger proteins (KZFPs) are one of the largest groups of transcription factors encoded by tetrapods, with 378 members in human alone. KZFP genes are often grouped in clusters reflecting amplification by gene and segment duplication since the gene family first emerged more than 400 million years ago. Previous work has revealed that many KZFPs recognize transposable element (TE)-embedded sequences as genomic targets, and that KZFPs facilitate the co-option of the regulatory potential of TEs for the benefit of the host. Here, we present a comprehensive survey of the genetic features and genomic targets of human KZFPs, notably completing past analyses by adding data on close to a hundred family members. General principles emerge from our study of the TE-KZFP regulatory system, which point to multipronged evolutionary mechanisms underlaid by highly complex and combinatorial modes of action with strong influences on human speciation.

摘要

Krüppel 相关盒 (KRAB) 结构域含有锌指蛋白 (KZFPs) 是脊椎动物编码的最大转录因子家族之一,仅人类就有 378 个成员。KZFP 基因通常聚类在一起,反映了自 4 亿多年前该基因家族首次出现以来通过基因和片段重复的扩增。先前的工作表明,许多 KZFPs 将转座元件 (TE) 嵌入序列识别为基因组靶标,并且 KZFPs 促进了 TE 的调控潜力被宿主利用。在这里,我们全面调查了人类 KZFPs 的遗传特征和基因组靶标,特别是通过添加近 100 个家族成员的数据来完成过去的分析。我们对 TE-KZFP 调控系统的研究得出了一些普遍原则,这些原则指出了多方面的进化机制,其作用方式非常复杂且组合多样,对人类的物种形成有很大的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec47/10547255/012b29376056/1409f01.jpg

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