The HML mating-type cassette of Saccharomyces cerevisiae is regulated by two separate but functionally equivalent silencers.

Mahoney, Deborah J.; Broach, James R.

doi:10.1128/mcb.9.11.4621

Cited by 98 publications

(105 citation statements)

References 63 publications

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“…The HML-E, HML-I, and HMR-E silencers have the ability to initiate silencing on their own, whereas HMR-I only plays an auxiliary role in silencing at the HMR locus (5,22,30,32). There is evidence that HMR-E is stronger than HML-E, which is stronger than HML-I, in silencing (34).…”

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confidence: 89%

Asymmetric Positioning of Nucleosomes and Directional Establishment of Transcriptionally Silent Chromatin by Saccharomyces cerevisiae Silencers

Zou

2006

Molecular and Cellular Biology

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In Saccharomyces cerevisiae, silencers flanking the HML and HMR loci consist of various combinations of binding sites for Abf1p, Rap1p, and the origin recognition complex (ORC) that serve to recruit the Sir silencing complex, thereby initiating the establishment of transcriptionally silent chromatin. There have been seemingly conflicting reports concerning whether silencers function in an orientation-dependent or -independent manner, and what determines the directionality of a silencer has not been explored. We demonstrate that chromatin plays a key role in determining the potency and directionality of silencers. We show that nucleosomes are asymmetrically distributed around the HML-I or HMR-E silencer so that a nucleosome is positioned close to the Abf1p side but not the ORC side of the silencer. This coincides with preferential association of Sir proteins and transcriptional silencing on the Abf1p side of the silencer. Elimination of the asymmetry in nucleosome positioning at a silencer leads to comparable silencing on both sides. Asymmetric nucleosome positioning in the immediate vicinity of a silencer is independent of its orientation and genomic context, indicating that it is the inherent property of the silencer. Moreover, it is also independent of the Sir complex and thus precedes the formation of silent chromatin. Finally, we demonstrate that asymmetric positioning of nucleosomes and directional silencing by a silencer depend on ORC and Abf1p. We conclude that the HML-I and HMR-E silencers promote asymmetric positioning of nucleosomes, leading to unequal potentials of transcriptional silencing on their sides and, hence, directional silencing.The establishment of condensed and transcriptionally silent heterochromatin in the eukaryotic genome is achieved via an initiation process that recruits silencing/repressor complexes to specific nucleation sequences, followed by their propagation along the chromatin. A silencing complex usually contains a histone-modifying enzyme(s) responsible for yielding heterochromatin-specific "histone codes" and structural proteins that recognize these codes and bind the modified histones with high affinity (13). In the yeast Saccharomyces cerevisiae, transcriptional silencing of the HML and HMR loci as well as regions near the telomeres is mediated by a silent chromatin that shares many similarities with metazoan heterochromatin at the molecular level (13). Silent chromatin at the HM loci is established by combined actions of cis-acting DNA elements and trans-acting proteins (32). The cis-acting elements are small specialized sequences, known as the E and I silencers, that flank the HM loci (Fig. 1A). Each silencer is composed of a unique combination of binding sites for proteins Abf1p, Rap1p, and ORC (for "origin recognition complex for DNA replication") (Fig. 1A), whose binding is required for silencing (32). The trans-acting factors include silencer-binding proteins, histones, and Sir1p through Sir4p. Sir2p is an NAD-dependent histone deacetylase that is believed to be resp...

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confidence: 89%

Asymmetric Positioning of Nucleosomes and Directional Establishment of Transcriptionally Silent Chromatin by Saccharomyces cerevisiae Silencers

Zou

2006

Molecular and Cellular Biology

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“…All strains used in this study were derived from DMY2 (MATa ura3-52 leu2-3,112 ade2-1 lys1-1 his5-2 can1-100 sir3TLEU2) (Mahoney and Broach 1989). Strains 101s-112s, 115s, 116s, 201s-205s, 210s-215s, 301s-307s, 401s-411s, and 501s-504s were constructed by transforming strain DMY2 to Ura 1 with BamHI-digested plasmids p101-p112, p115, p116, p201-p205, p210-215, p301-p307, p401-p411, and p501-p504, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…At the HMR locus, HMR-E can silence the HMRa genes on its own, whereas HMR-I plays no, or at most an auxiliary, role (Brand et al 1985;Rivier et al 1999). At the HML locus, on the other hand, either HML-E or HML-I alone is sufficient to silence the HMLa genes (Mahoney and Broach 1989). When ectopically inserted near the MAT locus, HMR-E was shown to be stronger than HML-E, which itself was stronger than HML-I in silencing activity (Shei and Broach 1995).…”

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confidence: 99%

Position Effect on the Directionality of Silencer Function in Saccharomyces cerevisiae

Zou

Chiu³

et al. 2006

Genetics

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In Saccharomyces cerevisiae, silencers flanking the HML and HMR loci initiate the establishment of transcriptional silencing. We demonstrate that the activity of a silencer pertaining to its potency and directionality is dependent on its genomic position. The context of the HML-E silencer is more permissive to silencer function than that of HML-I or HMR-E, despite that HML-E and HML-I are only 3.3 kb apart. The apparent strength and directionality of a silencer in a particular location is affected by other silencing elements (silencers and protosilencers) present in its context. We show that at the HML locus, at least four silencing elements engage in multiple functional interactions that contribute to the activities of the silencers. Notably, these dispersed silencing elements can synergize to silence genes located not only inside, but also outside the HML sequence that harbors them. Moreover, the relative positions and orientations of these elements are important for silencing, indicating that they belong to an intricate silencing network.

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“…Mutations of HMR-E that weaken silencing can be "tightened" by the presence of HMR-I. In contrast, either HML-E or HML-I is each sufficient to silence HML or other genes placed nearby (Mahoney and Broach 1989). Figure 3 Control of mating-type-specific genes.…”

Section: Cis-acting Silencer Sequencesmentioning

confidence: 99%

Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

2012

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Mating type in Saccharomyces cerevisiae is determined by two nonhomologous alleles, MATa and MATa. These sequences encode regulators of the two different haploid mating types and of the diploids formed by their conjugation. Analysis of the MATa1, MATa1, and MATa2 alleles provided one of the earliest models of cell-type specification by transcriptional activators and repressors. Remarkably, homothallic yeast cells can switch their mating type as often as every generation by a highly choreographed, site-specific homologous recombination event that replaces one MAT allele with different DNA sequences encoding the opposite MAT allele. This replacement process involves the participation of two intact but unexpressed copies of mating-type information at the heterochromatic loci, HMLa and HMRa, which are located at opposite ends of the same chromosome-encoding MAT. The study of MAT switching has yielded important insights into the control of cell lineage, the silencing of gene expression, the formation of heterochromatin, and the regulation of accessibility of the donor sequences. Real-time analysis of MAT switching has provided the most detailed description of the molecular events that occur during the homologous recombinational repair of a programmed double-strand chromosome break. TABLE OF CONTENTS Abstract 33Introduction 34

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The HML mating-type cassette of Saccharomyces cerevisiae is regulated by two separate but functionally equivalent silencers.

Cited by 98 publications

References 63 publications

Asymmetric Positioning of Nucleosomes and Directional Establishment of Transcriptionally Silent Chromatin by Saccharomyces cerevisiae Silencers

Asymmetric Positioning of Nucleosomes and Directional Establishment of Transcriptionally Silent Chromatin by Saccharomyces cerevisiae Silencers

Position Effect on the Directionality of Silencer Function in Saccharomyces cerevisiae

Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

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