Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.

IF 6.9 1区 生物学 Q1 CELL BIOLOGY
Jessica King, Stephen S Gisselbrecht, Julie-Alexia Dias, Raehoon Jeong, Elisabeth Rothman, Martha L Bulyk
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引用次数: 0

Abstract

Recognition of specific DNA sequences by transcription factors (TFs) is a key step in transcriptional control of gene expression. While most forkhead (FH) TFs bind either an FKH (RYAAAYA) or an FHL (GACGC) recognition motif, some FHs can bind both motifs. Mechanisms that control whether an FH is monospecific vs. bispecific have remained unknown. Screening a library of 12 reference FH proteins, 61 naturally occurring missense variants including clinical variants, and 22 designed mutant FHs for DNA-binding activity using universal ("all 10-mer") protein-binding microarrays revealed non-DNA-contacting residues that control mono- vs. bispecificity. Variation in non-DNA-contacting amino acid residues of TFs is associated with human traits and may play a role in the evolution of TF DNA-binding activities and gene regulatory networks.

人类叉头转录因子的错义变异揭示了叉头DNA双特异性的决定因素。
转录因子对特定DNA序列的识别是基因表达转录调控的关键步骤。虽然大多数叉头(FH) tf结合FKH (RYAAAYA)或FHL (GACGC)识别基序,但有些FH可以结合两个基序。控制FH是单特异性还是双特异性的机制仍然未知。使用通用(“所有10-mer”)蛋白质结合微阵列筛选12个参考FH蛋白库,61个自然存在的错义变体(包括临床变体)和22个设计突变FH的dna结合活性,发现非dna接触残基控制单特异性和双特异性。TF非dna接触氨基酸残基的变异与人类性状有关,可能在TF dna结合活性和基因调控网络的进化中发挥作用。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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