Direct integration of Hox and segmentation gene inputs during Drosophila development

Gebelein, Brian; McKay, Daniel J.; Mann, Richard S.

doi:10.1038/nature02946

Cited by 139 publications

(247 citation statements)

References 47 publications

Supporting

Mentioning

231

Contrasting

Unclassified

Order By: Relevance

“…However, in contrast to the effects seen on Dll expression, we did not found significant differences in binding affinities of Hox/ Exd complexes assembled through distinct interaction modes: Changing the balance from an HX-to a UbdA-dependent mode by modifying the LR in Cupiennius Ubx and AbdA proteins does not affect binding affinity significantly (Figs. S5 and S6); DmUbxIa and Dm-UbxIVa form Ubx/Exd complexes with similar affinities (21). These observations indicate that, in the case of Dll regulation, modifying the mode of interaction does not affect DNA binding.…”

Section: Discussionsupporting

confidence: 49%

“…To investigate whether these sequence divergences could affect the mode of Hox-Exd association, we performed in vitro band shift experiments, in which trimeric Ubx/Exd/Homothorax (Hth) complex formation on Dll target sequences relies on Ubx-Exd interaction (18,21). Mutations of either the HX or UbdA motifs were introduced in Ubx sequences.…”

Section: Arthropod Ubx Proteins Display Distinct Exd Interaction Modementioning

confidence: 99%

See 1 more Smart Citation

Selection of distinct Hox–Extradenticle interaction modes fine-tunes Hox protein activity

Saadaoui

Merabet

Litim-Mecheri

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Hox genes encode transcription factors widely used for diversifying animal body plans in development and evolution. To achieve functional specificity, Hox proteins associate with PBC class proteins, Pre-B cell leukemia homeobox (Pbx) in vertebrates, and Extradenticle (Exd) in Drosophila, and were thought to use a unique hexapeptide-dependent generic mode of interaction. Recent findings, however, revealed the existence of an alternative, UbdA-dependent paralog-specific interaction mode providing diversity in Hox-PBC interactions. In this study, we investigated the basis for the selection of one of these two Hox-PBC interaction modes. Using naturally occurring variations and mutations in the Drosophila Ultrabithorax protein, we found that the linker region, a short domain separating the hexapeptide from the homeodomain, promotes an interaction mediated by the UbdA domain in a context-dependent manner. While using a UbdA-dependent interaction for the repression of the limb-promoting gene Distalless, interaction with Exd during segment-identity specification still relies on the hexapeptide motif. We further show that distinctly assembled Hox-PBC complexes display subtle but distinct repressive activities. These findings identify Hox-PBC interaction as a template for subtle regulation of Hox protein activity that may have played a major role in the diversification of Hox protein function in development and evolution.transcriptional regulation | AbdominalA | Hox protein specificity and diversity

show abstract

Section: Discussionsupporting

confidence: 49%

Section: Arthropod Ubx Proteins Display Distinct Exd Interaction Modementioning

confidence: 99%

Selection of distinct Hox–Extradenticle interaction modes fine-tunes Hox protein activity

Saadaoui

Merabet

Litim-Mecheri

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Among them, there should be factors that relate the appendage-determining genes to the Hox selector genes, which are responsible for the anteroposterior diversity of the adult segments. Such links are only now being discovered (Gebelein et al 2004). These selector genes also need to cooperate with signaling factors (Grieder et al 1997;reviewed in Affolter and Mann 2001).…”

mentioning

confidence: 99%

Misexpression Screen in Drosophila melanogaster Aiming to Reveal Novel Factors Involved in Formation of Body Parts

et al. 2007

View full text Add to dashboard Cite

To identify novel factors that lead a fly imaginal disc to adopt its developmental fate, we carried out a modular dominant misexpression screen in imaginal discs. We have identified two factors that appear to change the fate of the respective body structure and appear to lead to the transformation of a body part. In one mutant line, notum tissue, normally derived from wing imaginal tissue, formed close to the site of the sternopleural bristles, which are leg disc derivatives. In the other line, the arista is transformed into a tubular structure, resembling an abnormal leg. We found that ectopic expression of abrupt was responsible for this potential transformation of the arista.

show abstract

“…Classically, these two processes have been thought to occur independently. Analysis of Distalless-a Hox target gene-using enhancer-reporter constructs by Gebelein et al (2004) reveals a previously unanticipated use of compartments for gene regulation by Hox proteins. Their results suggest that these segmentation and Hox gene products may collaborate to directly control gene expression of many downstream target genes.…”

Section: Research Commentarymentioning

confidence: 99%

Discrimination in partnership: compartment-specific interactions of Hox proteins

Guruharsha

VijayRaghavan

2004

J Genet

View full text Add to dashboard Cite

A relatively small number of regulatory proteins perform multiple functions to orchestrate the development of an animal from a zygote. Many regulatory proteins are transcription factors that affect the expression of downstream genes. These factors interact with other proteins in the nucleus to regulate expression of their target genes. The main effect of loss-of-function mutations in genes encoding major regulators of development is lethality at the earliest stage where the regulatory molecule is required. Many, very important roles of regulatory factors have been inferred from these lethal phenotypes. However, the early lethality means that understanding the later roles, if any, of such genes becomes difficult. In addition, loss-offunction studies alone do not usually provide insights into the identity and role of interacting proteins critical for the final output of the regulatory signal.Till recently, much of the focus in genomic research was on understanding gene sequences and function. These studies showed that important regulatory proteins are highly conserved in sequence and, often, in function, in organisms as diverse as mice and worms. Thus, novel genes alone do not make one organism different from another. Instead, many findings have made it clear that the difference between species very likely arises from the function of regulatory sequences that determine the time and pattern of gene expression. These patterns of gene expression define a diversity of cellular functions during development, which in turn allows, again through regulation of gene expression and by epigenetic mechanisms, further refinement of the pathways of development in each organism (see Pennisi 2004 for example).The regulated expression of a gene is thus a consequence of a fine balance between two components: (i) trans-acting factors-these are transcription factors/regulatory proteins with specific affinity for each other and for target DNA sequences; and (ii) the targets of these factors or the cis-regulatory DNA which responds to the trans-acting factors by allowing or repressing gene expression. In other words, the binding of specific transcription factors to the combinatorial code of cis-regulatory elements brings about activation or repression of target genes (Arnone and Davidson, 1997, Ghazi andVijayRaghavan 2000).Researchers have found new and efficient ways to locate regulatory regions distributed in the genome. Enhancers-stretches of DNA that harbor cis-regulatory elements-have been identified for some years now in model organisms such as Drosophila by examining how these regulatory sequences affect reporter gene expression. These studies have rapidly deciphered different mechanisms by which transcription factors and other proteins interact with regulatory DNA and with each other to guide gene activity. Reporter studies of gene enhancers with precise alterations in putative binding sites for different transcription factors in an otherwise wild-type background answer questions on gene regulation at greater resolution. These s...

show abstract

Direct integration of Hox and segmentation gene inputs during Drosophila development

Cited by 139 publications

References 47 publications

Selection of distinct Hox–Extradenticle interaction modes fine-tunes Hox protein activity

Selection of distinct Hox–Extradenticle interaction modes fine-tunes Hox protein activity

Misexpression Screen in Drosophila melanogaster Aiming to Reveal Novel Factors Involved in Formation of Body Parts

Discrimination in partnership: compartment-specific interactions of Hox proteins

Contact Info

Product

Resources

About