RAP-1 factor is necessary for DNA loop formation in vitro at the silent mating type locus HML

Hofmann, Johannes; Laroche, Thierry; Brand, Andrea H.; Gasser, Susan M.

doi:10.1016/0092-8674(89)90788-5

Cited by 191 publications

(103 citation statements)

References 43 publications

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“…Rap1p might also aid long-range communication. When bound to two sites on naked DNA, the protein induces loop formation (31). Further experiments will be necessary to dissect the roles of these elements and proteins in long-range communication.…”

Section: Discussionmentioning

confidence: 99%

Long-Range Communication between the Silencers of HMR

Valenzuela

Dhillon

Dubey

et al. 2008

Molecular and Cellular Biology

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Gene regulation involves long-range communication between silencers, enhancers, and promoters. In Saccharomyces cerevisiae, silencers flank transcriptionally repressed genes to mediate regional silencing. Silencers recruit the Sir proteins, which then spread along chromatin to encompass the entire silenced domain. In this report we have employed a boundary trap assay, an enhancer activity assay, chromatin immunoprecipitations, and chromosome conformation capture analyses to demonstrate that the two HMR silencer elements are in close proximity and functionally communicate with one another in vivo. We further show that silencing is necessary for these long-range interactions, and we present models for Sir-mediated silencing based upon these results.Gene activation and gene repression are central to the proper development and differentiation of organisms. DNA elements such as promoters, enhancers, and silencers play a central role in eukaryotic gene regulation. These elements are separated from each other by several kilobase pairs of DNA but are able to communicate with one another to regulate the activation or repression of genes. The exact mechanism by which distally located elements communicate with one another is not clear and is one of the key questions in gene regulation. Long-range communication between distantly located elements in chromosomes is thought to occur by one of two principal mechanisms (8). One class of models postulate that a signal emanating from a distal regulatory element spreads along the DNA fiber until it encounters a proximal regulatory element. A second class of models postulate that distal and proximal regulatory elements interact with one another directly, with the intervening DNA forming a loop. Both mechanisms must function within the context of the global chromosome structure, which appears to be composed of large chromosome loops that attach to a proteinaceous superstructure (11). The nucleus appears to be divided further into distinct chromatin compartments, with heterochromatic domains being present in regions near the nuclear periphery while euchromatic domains are found mainly in the interior of the nucleus, although a significant portion of euchromatin is located near nuclear pores.It has been suggested that the functionally and structurally defined chromatin domains may be coincident (36). Enhancers and locus control regions (LCRs) are long-range regulatory elements that activate promoters in a distance-and orientation-independent manner, and recent studies indicate that enhancers and LCRs often cluster together in three-dimensional space to form an "active chromatin hub" (23,49,58,59).Similarly, in yeast the promoters and terminators of genes are in close proximity to one another (3, 48) and tethered to the nuclear pore (10, 52). The consequence of this spatial organization is that the DNA between these regulatory elements is looped out. It is thought that the formation of these nuclear substructures aids in transcription activation.Silencers are negative regulatory element...

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Section: Discussionmentioning

confidence: 99%

Long-Range Communication between the Silencers of HMR

Valenzuela

Dhillon

Dubey

et al. 2008

Molecular and Cellular Biology

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“…It has been proposed that attachment of silencer DNA to the nuclear scaffold forms a domain within which changes in chromatin structure occur, thereby rendering a locus transcriptionally inactive (Hofmann et al, 1989). In the yeast mating type HML locus, the silencer E site binds RAP-1, a protein which appears to mediate DNA loop formation and attachment to the nuclear matrix in reconstitution experiments (Hofmann et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal-mediated repression in Drosophila

Kirov¹,

Zhelnin²,

Shah³

et al. 1993

Trends in Genetics

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“…At present the exact nature of the mechanism by which silencers exert negative transcriptional control is not known. Silencers may involve a conformational change, such as DNA looping, to disorganize the transcriptional initiation complex (17,43) or binding of a specific protein to the DNA silencer sequence to 'lock' the transcriptional start site (19).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a silencer element in the first exon of the human osteocalcin gene

Chen²,

Stashenko³

1995

Nucl Acids Res

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Osteocalcin, the major non-collagenous protein in bone, is transcribed in osteoblasts at the onset of extracellular matrix mineralization. In this study It was demonstrated that sequences located in the first exon of the human osteocalcin gene possess a differentiation-related osteocalcin silencer element (OSE). Osteocalcin was rendered transcribable in UMR-106 cells and proliferating normal osteoblasts after deletion of the -3 to +51 region. Site-specific mutagenesis of this region revealed that a 7 bp sequence (TGGCCCT) (+29 to +35) is critcal for silencing function. Mobility shift assays demonstrated that a nuclear factor bound to the OSE. The OSE binding protein was present in proliferating normal pre-osteoblasts and in UMR-106 and ROS 17/2.8 osteosarcoma cells, but was absent from post-proliferative normal osteoblasts. The binding protein was inhibited by fragments containing the +29/+35 sequence, but not by other promoter fragments or by the consensus oligomers of unrelated nuclear factors AP-1 and Spl. DNase I footprinting demonstrated that the OSE binding-protein protected the +17 to +36 portion of the first exon, consistent with the results of mapping studies and competitive mobility shift assays. It Is hypothesized that this silencer is activated by complexing of the OSE binding protein to the OSE during the osteoblast proliferation stage and that the OSE binding protein is down-regulated at the onset of extracellular matrix mineralization.

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RAP-1 factor is necessary for DNA loop formation in vitro at the silent mating type locus HML

Cited by 191 publications

References 43 publications

Long-Range Communication between the Silencers of HMR

Long-Range Communication between the Silencers of HMR

Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal-mediated repression in Drosophila

Characterization of a silencer element in the first exon of the human osteocalcin gene

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