Homeodomain complex formation and biomolecular condensates in Hox gene regulation.

Autor: Salomone J; Graduate Program in Molecular and Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA; Medical-Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA., Farrow E; Graduate Program in Molecular and Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA; Medical-Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA., Gebelein B; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 7007, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: Brian.Gebelein@cchmc.org.
Jazyk: angličtina
Zdroj: Seminars in cell & developmental biology [Semin Cell Dev Biol] 2024 Jan-Feb; Vol. 152-153, pp. 93-100. Date of Electronic Publication: 2022 Dec 12.
DOI: 10.1016/j.semcdb.2022.11.016
Abstrakt: Hox genes are a family of homeodomain transcription factors that regulate specialized morphological structures along the anterior-posterior axis of metazoans. Over the past few decades, researchers have focused on defining how Hox factors with similar in vitro DNA binding activities achieve sufficient target specificity to regulate distinct cell fates in vivo. In this review, we highlight how protein interactions with other transcription factors, many of which are also homeodomain proteins, result in the formation of transcription factor complexes with enhanced DNA binding specificity. These findings suggest that Hox-regulated enhancers utilize distinct combinations of homeodomain binding sites, many of which are low-affinity, to recruit specific Hox complexes. However, low-affinity sites can only yield reproducible responses with high transcription factor concentrations. To overcome this limitation, recent studies revealed how transcription factors, including Hox factors, use intrinsically disordered domains (IDRs) to form biomolecular condensates that increase protein concentrations. Moreover, Hox factors with altered IDRs have been associated with altered transcriptional activity and human disease states, demonstrating the importance of IDRs in mediating essential Hox output. Collectively, these studies highlight how Hox factors use their DNA binding domains, protein-protein interaction domains, and IDRs to form specific transcription factor complexes that yield accurate gene expression.
Competing Interests: Conflicts of Interest None
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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