Functional Requirements for <i>Fab-7</i> Boundary Activity in the Bithorax Complex

Wolle, Daniel; Cleard, Fabienne; Aoki, Tsutomu; Deshpande, Girish; Schedl, Paul; Karch, François

doi:10.1128/mcb.00456-15

Cited by 55 publications

(127 citation statements)

References 95 publications

(125 reference statements)

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“…Overall, the known Drosophila insulator proteins can be divided into three groups based on their biochemical and functional properties. The first group contains sequence-specific DNA binding proteins: Su(Hw), CTCF, BEAF-32, Ibf1, Ibf2, Pita, ZIPIC (also known as CG7928), Dwg, and GAF (the product of the Trithorax-like gene) (Geyer and Corces 1992; Zhao et al 1995; Gaszner et al 1999; Moon et al 2005; Cuartero et al 2014; Maksimenko et al 2015; Wolle et al 2015). The second group consists of the Cp190 protein and multiple protein isoforms encoded by the mod ( mdg4 ) gene (Dorn et al 2001; Pai et al 2004; Van Bortle et al 2012).…”

Section: Defining the Borders Of Topological And Functional Chromosommentioning

confidence: 99%

Three-Dimensional Genome Organization and Function in Drosophila

Schwartz

Cavalli

2017

Genetics

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Understanding how the metazoan genome is used during development and cell differentiation is one of the major challenges in the postgenomic era. Early studies in Drosophila suggested that three-dimensional (3D) chromosome organization plays important regulatory roles in this process and recent technological advances started to reveal connections at the molecular level. Here we will consider general features of the architectural organization of the Drosophila genome, providing historical perspective and insights from recent work. We will compare the linear and spatial segmentation of the fly genome and focus on the two key regulators of genome architecture: insulator components and Polycomb group proteins. With its unique set of genetic tools and a compact, well annotated genome, Drosophila is poised to remain a model system of choice for rapid progress in understanding principles of genome organization and to serve as a proving ground for development of 3D genome-engineering techniques.

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Section: Defining the Borders Of Topological And Functional Chromosommentioning

confidence: 99%

Three-Dimensional Genome Organization and Function in Drosophila

Schwartz

Cavalli

2017

Genetics

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“…One example of a boundary that is composed of multiple functionally redundant elements is Fab-7 from the Drosophila bithorax complex (BX-C) Wolle et al 2015). BX-C contains three homeotic genes, Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B).…”

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confidence: 99%

The BEN Domain Protein Insensitive Binds to the Fab-7 Chromatin Boundary To Establish Proper Segmental Identity in Drosophila

et al. 2018

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Boundaries (insulators) in the Drosophila bithorax complex (BX-C) delimit autonomous regulatory domains that orchestrate the parasegment (PS)-specific expression of the BX-C homeotic genes. The Fab-7 boundary separates the iab-6 and iab-7 regulatory domains, which control Abd-B expression in PS11 and PS12, respectively. This boundary is composed of multiple functionally redundant elements and has two key functions: it blocks cross talk between iab-6 and iab-7 and facilitates boundary bypass. Here, we show that two BEN domain protein complexes, Insensitive and Elba, bind to multiple sequences located in the Fab-7 nuclease hypersensitive regions. Two of these sequences are recognized by both Insv and Elba and correspond to a CCAATTGG palindrome. Elba also binds to a related CCAATAAG sequence, while Insv does not. However, the third Insv recognition sequences is 100 bp in length and contains the CCAATAAG sequence at one end. Both Insv and Elba are assembled into large complexes (420 and 265-290 kDa, respectively) in nuclear extracts. Using a sensitized genetic background, we show that the Insv protein is required for Fab-7 boundary function and that PS11 identity is not properly established in insv mutants. This is the first demonstration that a BEN domain protein is important for the functioning of an endogenous fly boundary.

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“…Based on their biochemical and functional properties, the known Drosophila insulator proteins can be divided in three groups. The first group consists of nine sequence-specific DNA binding proteins: Su(Hw), CTCF, BEAF-32, Ibf1, Ibf2, Pita, ZIPIC (also known as CG7928), Dwg (also known as Zw5), and GAF (the product of Trithorax-like gene) (Geyer and Corces 1992;Zhao et al 1995;Gaszner et al 1999;Schweinsberg et al 2004; Copyright © 2016 Moon Cuartero et al 2014;Maksimenko et al 2015;Wolle et al 2015). The second group includes Cp190 and multiple protein isoforms encoded by the mod(mdg4) gene (Dorn et al 2001;Pai et al 2004;.…”

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confidence: 99%

Distinct Roles of Chromatin Insulator Proteins in Control of the Drosophila Bithorax Complex

et al. 2015

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Chromatin insulators are remarkable regulatory elements that can bring distant genomic sites together and block unscheduled enhancer-promoter communications. Insulators act via associated insulator proteins of two classes: sequence-specific DNA binding factors and "bridging" proteins. The latter are required to mediate interactions between distant insulator elements. Chromatin insulators are critical for correct expression of complex loci; however, their mode of action is poorly understood. Here, we use the Drosophila bithorax complex as a model to investigate the roles of the bridging proteins Cp190 and Mod(mdg4). The bithorax complex consists of three evolutionarily conserved homeotic genes Ubx, abd-A, and Abd-B, which specify anterior-posterior identity of the last thoracic and all abdominal segments of the fly. Looking at effects of CTCF, mod(mdg4), and Cp190 mutations on expression of the bithorax complex genes, we provide the first functional evidence that Mod(mdg4) acts in concert with the DNA binding insulator protein CTCF. We find that Mod(mdg4) and Cp190 are not redundant and may have distinct functional properties. We, for the first time, demonstrate that Cp190 is critical for correct regulation of the bithorax complex and show that Cp190 is required at an exceptionally strong Fub insulator to partition the bithorax complex into two topological domains.KEYWORDS HOX genes; chromatin; chromatin insulators; Drosophila; gene regulation T HE eukaryotic genome is folded extensively to fit inside the cell nucleus. The folding patterns vary between individual cells but certain conformations occur more frequently. In some cases, the likelihood of acquiring a particular conformation is linked to activation or repression of specific genes. Such links are especially important for complex loci in which multiple regulatory elements are positioned tens of thousands of base pairs (kb) away from their target promoters. The Drosophila bithorax complex is one of the best studied complex loci. The bithorax complex consists of three evolutionarily conserved homeotic genes Ubx, abd-A, and Abd-B that encode transcription factors and specify anterior-posterior identity of the last thoracic and all abdominal segments of the fly . Segment-specific expression of the bithorax complex genes is controlled by distal transcriptional enhancers and polycomb/trithorax response elements (PRE/TREs). The correct function of enhancers and PREs/ TREs is further orchestrated by chromatin insulator elements that modulate the topology of the bithorax complex by mechanisms that are not well understood.Chromatin insulator elements were first discovered in Drosophila and later found in vertebrates and plants. They are short (1 kb) DNA elements that can block ("insulate") transcriptional activation of a promoter by a remote enhancer when interposed between the two. In contrast to transcriptional repression, insulation leaves the promoter transcriptionally competent so it is free to engage with other enhancers as long as those are not sepa...

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Functional Requirements for Fab-7 Boundary Activity in the Bithorax Complex

Cited by 55 publications

References 95 publications

Three-Dimensional Genome Organization and Function in Drosophila

Three-Dimensional Genome Organization and Function in Drosophila

The BEN Domain Protein Insensitive Binds to the Fab-7 Chromatin Boundary To Establish Proper Segmental Identity in Drosophila

Distinct Roles of Chromatin Insulator Proteins in Control of the Drosophila Bithorax Complex

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