Formation of Boundaries of Transcriptionally Silent Chromatin by Nucleosome-Excluding Structures

Bi, Xin; Yu, Qun; Sandmeier, Joseph J.; Zou, Yanfei

doi:10.1128/mcb.24.5.2118-2131.2004

Cited by 77 publications

(100 citation statements)

References 54 publications

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“…Specifically, we envision that the nucleosome positioned close to the Abf1p side of the silencer allows or facilitates the Sir complex to start spreading on this side, whereas the lack of a stably positioned nucleosome adjacent to the ORC site reduces the efficiency of initiation of Sir propagation on this side. This hypothesis is based on the fact that nucleosomes are both the substrates for the histone deacetylase activity of the Sir complex and also the platform for Sir recruitment, according to the current view of the nucleosome-by-nucleosome propagation of Sir complexes along chromatin (3,13,32). In support of this contention, we have demonstrated that Sir3p preferentially associates with sequences on the Abf1p side of the HMR-E silencer (Fig.…”

Section: Discussionsupporting

confidence: 63%

“…In this manner, the Sir complex is thought to promote its own stepwise (nucleosomeby-nucleosome) propagation along a continuous array of nucleosomes, thereby establishing an extended region of silent chromatin (13). This model is supported by our finding that disrupting the regularity of nucleosomes by nucleosome-excluding structures hinders the spread of silent chromatin (3).…”

supporting

confidence: 77%

“…Propagation of Sir complexes on May 11, 2018 by guest http://mcb.asm.org/ along the chromatin depends on their association with nucleosomes and presumably requires a continuous array of closely positioned nucleosomes (3,32). Given that Abf1p, Rap1p, and ORC all have the ability to modulate local chromatin structure upon binding to DNA (3,20,41,42), we envisioned that nucleosomes might be organized differently (asymmetrically) on the flanks of HML-I and HMR-E, resulting in unequal potentials for the spread of Sir proteins on the two sides. To test this hypothesis, we mapped nucleosomes around HML-I and HMR-E using micrococcal nuclease (MNase) digestion and indirect end labeling (33).…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 63%

supporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

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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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“…Although the borders of the DNase I-hypersensitive site I were not mapped except for the upstream border on the upper strand, the analysis of the lower strand revealed that the hypersensitive region included at least 250 bases. This extensive region of hypersensitivity is probably nucleosome-free (30), and it has been proposed that the absence of nucleosomes from insulators is important for their function (33,34). Within the hypersensitivite site, there were two cold spots or areas of relative resistance around the CCAAT box and around the CTCF binding motif but not around the thyroid hormone response element.…”

Section: Resultsmentioning

confidence: 99%

Chromatin fine structure of the c- MYC insulator element/DNase I-hypersensitive site I is not preserved during mitosis

Komura

Ikehata²,

Ono³

2007

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

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During mitosis in higher eukaryotic cells, transcription is silenced and transcription complexes are absent from promoters in the condensed chromosomes; however, epigenetic information concerning the pattern of expressed and silent genes must be preserved. Recently, it has been reported that CTCF, a major protein in vertebrate insulator elements, remains associated with mitotic chromatin. If the structure of insulators is preserved during mitosis, then it is possible that insulators can function as components or elements of the mechanism involved in the transfer of epigenetic information through the mitotic phase and can help guide the reconstitution of domain structure and nuclear organization after the completion of this phase. We have studied the chromatin structure of the insulator upstream of the c-MYC gene in mitotic HeLa cells. The region of the insulator corresponds to the DNase I hypersensitive site I, but Southern blot analysis revealed that hypersensitivity was lost during mitosis. High resolution in vivo footprinting analysis using dimethyl sulfate, UV light, psoralen, and DNase I also demonstrated the disappearance of the sequencespecific direct binding of CTCF and the absence of detectable structures during mitosis. Thus, it appears that the nucleoprotein complex involving this insulator element must be reassembled de novo with each new cell generation.epigenetics ͉ in vivo footprinting

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“…The mechanism by which such spreading is blocked has been attributed to targeted recruitment of HAT activity to boundary elements, with histone acetylation acting as a chain terminator for the heterochromatic modification pattern. An alternative model proposes that a short (100 -300 bp) nucleosome-free region is formed at the boundary, which the processive mechanism of heterochromatin spreading cannot span (39).…”

Section: Minireview: Formation and Function Of Hyperacetylated Domainmentioning

confidence: 99%

Hyperacetylated Chromatin Domains: Lessons from Heterochromatin

Bulger

2005

Journal of Biological Chemistry

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A small but growing number of loci that exhibit covalent histone modifications, such as hyperacetylation, over broad regions of 10 kb or more have been characterized. These hyperacetylated domains occur exclusively at loci containing highly expressed, tissue-specific genes, and the available evidence suggests that they are involved in the activation of these genes. Although to date little is known concerning the formation or function of these domains, rather more is known concerning repressive, heterochromatic domains, and the example provided by heterochromatin may be instructive in considering mechanisms of active domain formation.In eukaryotes, genomic DNA is packaged with histones to form chromatin, which in turn condenses to form more compact structures (1, 2). The condensation of chromatin has an obvious impact on any process, such as transcription, replication, DNA repair, or recombination, requiring access to genomic DNA, and not surprisingly a wide array of studies has shown that chromatin structure plays a crucial role in the regulation of all of these processes. In particular, transcriptional regulation involves the modification of chromatin structure as a necessary step in the establishment and maintenance of active or repressed states. A common mechanism of modifying chromatin structure is the covalent addition (or removal) of acetyl, methyl, phosphoryl, or other moieties to the amino-terminal tail domains of the core histones by specific enzymes. For example, nucleosomes near active gene promoters and enhancers are nearly always acetylated, due to the recruitment of histone acetyltransferases (HATs) 1 by transcription factors.

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Formation of Boundaries of Transcriptionally Silent Chromatin by Nucleosome-Excluding Structures

Cited by 77 publications

References 54 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

Chromatin fine structure of the c- MYC insulator element/DNase I-hypersensitive site I is not preserved during mitosis

Hyperacetylated Chromatin Domains: Lessons from Heterochromatin

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