Related Experiment Video
Updated: Jun 10, 2026
10:10
HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
Dissecting the functional specificities of two Hox proteins
Rohit Joshi1, Liping Sun, Richard Mann
1Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032, USA.
Genes & Development
|July 17, 2010
Summary
Hox proteins like Deformed (Dfd) use cofactors to bind DNA specifically. Subtle differences in binding and non-DNA domains dictate gene activation or repression, revealing a general mechanism for Hox protein function.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Hox proteins are crucial transcription factors regulating embryonic development.
- Cofactors such as Extradenticle (Exd) are essential for Hox protein DNA binding specificity.
- Previous studies showed Sex combs reduced (Scr) uses Exd to bind DNA minor grooves.
Purpose of the Study:
- To investigate if Deformed (Dfd) Hox protein utilizes a similar cofactor-dependent DNA binding mechanism as Scr.
- To elucidate how DNA binding site recognition and non-DNA binding domains influence transcriptional output.
- To generalize the mechanism of Hox-cofactor-DNA ternary complex formation and its regulatory consequences.
Main Methods:
- Comparative analysis of Hox protein (Scr and Dfd) DNA binding interactions.
- In vivo studies in Drosophila melanogaster.
- Investigation of ternary complex architecture and its effect on coactivator/corepressor recruitment.
Main Results:
- Deformed (Dfd) Hox protein employs a mechanism analogous to Scr, using Exd to insert basic residues into DNA minor grooves for specific binding.
- Subtle variations in DNA binding site recognition by Dfd and Scr, coupled with their non-DNA binding domains, determine target gene activation or repression.
- The specific architecture of the Hox-cofactor-DNA ternary complex dictates the recruitment of transcriptional coactivators or corepressors.
Conclusions:
- The cofactor-mediated DNA binding mechanism is a general feature of Hox protein specificity.
- Hox protein function is fine-tuned by the interplay between DNA binding site recognition, cofactor interaction, and non-DNA binding domains.
- The structure of the ternary complex is a key determinant of transcriptional regulation by Hox proteins.
Related Concept Videos
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
01:30General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:45The Ratio of X Chromosome to Autosomes
In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
02:33Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...