دورية أكاديمية
A Twist-Box domain of the C. elegans Twist homolog, HLH-8, plays a complex role in transcriptional regulation.
| العنوان: | A Twist-Box domain of the C. elegans Twist homolog, HLH-8, plays a complex role in transcriptional regulation. |
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| المؤلفون: | Gruss MJ; Department of Biology, The Catholic University of America, 620 Michigan Ave., NE, Washington, D.C. 20064USA., O'Callaghan C; Department of Biology, The Catholic University of America, 620 Michigan Ave., NE, Washington, D.C. 20064USA., Donnellan M; Department of Biology, The Catholic University of America, 620 Michigan Ave., NE, Washington, D.C. 20064USA., Corsi AK; Department of Biology, The Catholic University of America, 620 Michigan Ave., NE, Washington, D.C. 20064USA. |
| المصدر: | Genetics [Genetics] 2023 Aug 09; Vol. 224 (4). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0374636 Publication Model: Print Cited Medium: Internet ISSN: 1943-2631 (Electronic) Linking ISSN: 00166731 NLM ISO Abbreviation: Genetics Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [Oxford] : Oxford University Press Original Publication: Austin, Tex. [etc.] |
| مواضيع طبية MeSH: | Acrocephalosyndactylia*/genetics , Acrocephalosyndactylia*/metabolism , Caenorhabditis elegans*/genetics , Caenorhabditis elegans*/metabolism, Animals ; Female ; Humans ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Mutation ; Transcription Factors/genetics ; Twist-Related Protein 1/genetics ; Twist-Related Protein 1/chemistry ; Twist-Related Protein 1/metabolism |
| مستخلص: | TWIST1 is a basic helix-loop-helix (bHLH) transcription factor in humans that functions in mesoderm differentiation. TWIST1 primarily regulates genes as a transcriptional repressor often through TWIST-Box domain-mediated protein-protein interactions. The TWIST-Box also can function as an activation domain requiring 3 conserved, equidistant amino acids (LXXXFXXXR). Autosomal dominant mutations in TWIST1, including 2 reported in these conserved amino acids (F187L and R191M), lead to craniofacial defects in Saethre-Chotzen syndrome (SCS). Caenorhabditis elegans has a single TWIST1 homolog, HLH-8, that functions in the differentiation of the muscles responsible for egg laying and defecation. Null alleles in hlh-8 lead to severely egg-laying defective and constipated animals due to defects in the corresponding muscles. TWIST1 and HLH-8 share sequence identity in their bHLH regions; however, the domain responsible for the transcriptional activity of HLH-8 is unknown. Sequence alignment suggests that HLH-8 has a TWIST-Box LXXXFXXXR motif; however, its function also is unknown. CRISPR/Cas9 genome editing was utilized to generate a domain deletion and several missense mutations, including those analogous to SCS patients, in the 3 conserved HLH-8 amino acids to investigate their functional role. The TWIST-Box alleles did not phenocopy hlh-8 null mutants. The strongest phenotype detected was a retentive (Ret) phenotype with late-stage embryos in the hermaphrodite uterus. Further, GFP reporters of HLH-8 downstream target genes (arg-1::gfp and egl-15::gfp) revealed tissue-specific, target-specific, and allele-specific defects. Overall, the TWIST-Box in HLH-8 is partially required for the protein's transcriptional activity, and the conserved amino acids contribute unequally to the domain's function. Competing Interests: Conflicts of interest The author(s) declare no conflict of interest. (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) |
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| معلومات مُعتمدة: | P40 OD010440 United States OD NIH HHS; R15 DE018519 United States DE NIDCR NIH HHS |
| فهرسة مساهمة: | Keywords: C. elegans; HLH-8; Saethre–Chotzen syndrome; TWIST1; Twist-Box domain; tissue-specific transcriptional regulation |
| المشرفين على المادة: | 0 (Basic Helix-Loop-Helix Transcription Factors) 0 (Transcription Factors) 0 (Twist-Related Protein 1) 0 (HLH-8 protein, C elegans) |
| تواريخ الأحداث: | Date Created: 20230417 Date Completed: 20230810 Latest Revision: 20240418 |
| رمز التحديث: | 20240418 |
| مُعرف محوري في PubMed: | PMC10411555 |
| DOI: | 10.1093/genetics/iyad066 |
| PMID: | 37067863 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1943-2631 |
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| DOI: | 10.1093/genetics/iyad066 |