Histones Are First Hyperacetylated and Then Lose Contact with the Activated PHO5 Promoter

Reinke, Hans; Hörz, Wolfram

doi:10.1016/s1097-2765(03)00186-2

Cited by 374 publications

(358 citation statements)

References 43 publications

Supporting

Mentioning

303

Contrasting

Unclassified

Order By: Relevance

“…Recruitment is mediated either by activator proteins bound at promoter regions (17)(18)(19)(20)(21) or by elongating Pol II (and associated factors) at highly transcribed genes (21-24). We presume that the nucleosome-remodeling complexes and/or histone chaperones responsible for rapid histone exchange differ from those used during DNA replication.…”

Section: Relative Ip Efficiencymentioning

confidence: 99%

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

Katan-Khaykovich

Struhl

2011

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

View full text Add to dashboard Cite

Nucleosome deposition occurs on newly synthesized DNA during DNA replication and on transcriptionally active genes via nucleosome-remodeling complexes recruited by activator proteins and elongating RNA polymerase II. It has been long believed that histone deposition involves stable H3-H4 tetramers, such that newly deposited nucleosomes do not contain H3 and H4 molecules with their associated histone modifications from preexisting nucleosomes. However, biochemical analyses and recent experiments in mammalian cells have raised the idea that preexisting H3-H4 tetramers might split into dimers, resulting in mixed nucleosomes composed of "old" and "new" histones. It is unknown to what extent different genomic loci might utilize such a mechanism and under which circumstances. Here, we address whether tetramer splitting occurs in a locus-specific manner by using sequential chromatin immunoprecipitation of mononucleosomes from yeast cells containing two differentially tagged versions of H3 that are expressed "old" and "new" histones. At many genomic loci, we observe little or no nucleosomal cooccupancy of old and new H3, indicating that tetramer splitting is generally infrequent. However, cooccupancy is detected at highly active genes, which have a high rate of histone exchange. Thus, DNA replication largely results in nucleosomes bearing exclusively old or new H3-H4, thereby precluding the acquisition of new histone modifications based on preexisting modifications within the same nucleosome. In contrast, tetramer splitting, dimer exchange, and nucleosomes with mixed H3-H4 tetramers occur at highly active genes, presumably linked to rapid histone exchange associated with robust transcription.T he packaging of eukaryotic DNA into chromatin influences many DNA-associated processes, including transcriptional regulation. Within the chromatin fiber, each basic nucleosome unit bears important chemical and structural information. The mechanisms by which nucleosomes are assembled on DNA during replication, transcription, DNA repair, etc., can thus impact not only the integrity of chromatin structure but also patterns of gene expression and epigenetic inheritance. The H3-H4 tetramer core of each nucleosome is the more stable component and contains most of the relatively persistent and functionally important histone methylation marks. Much attention has therefore been given to the questions of how the H3-H4 tetramers are formed and maintained on chromatin.Early studies attempted to distinguish between a conservative assembly model, by which old and new histones form separate tetramers on replicating DNA, and a semiconservative assembly mechanism, by which existing tetramers are split into H3-H4 dimers, followed by association of new H3-H4 dimers to complete each nucleosome core (1-3). In the semiconservative model, the resulting tetramers would bear a mixture of old and new histones, allowing transmission of epigenetic information within the basic nucleosome unit. Though mechanistically attractive, the mixed tetramer model receiv...

show abstract

Section: Relative Ip Efficiencymentioning

confidence: 99%

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

Katan-Khaykovich

Struhl

2011

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

View full text Add to dashboard Cite

show abstract

“…1): (i) sliding, or moving the histone octamer to a new position, which exposes DNA 10-12 ; (ii) ejection, or completely displacing the octamer to expose DNA [13][14][15][16] ; (iii) removal of H2A-H2B dimers, leaving only the central H3-H4 tetramer, which exposes DNA and destabilizes the nucleosome 17,18 ; and (iv) dimer replacement-for example, exchanging the resident H2A-H2B dimers for dimers NIH Public Access…”

Section: Remodelers Slide Eject and Restructure Nucleosomesmentioning

confidence: 99%

“…Studies of the yeast PHO5 gene suggest that nucleosomes are removed from the promoter upon activation 15,16 . Interestingly, genomewide analyses show that promoters are intrinsically nucleosome deficient and become more deficient during activation 73,74 .…”

Section: Nucleosome Ejection: Pulling the Rug From Under Your Neighbor?mentioning

confidence: 99%

Chromatin remodeling: insights and intrigue from single-molecule studies

Cairns

2007

Nat Struct Mol Biol

226

208

View full text Add to dashboard Cite

Chromatin remodelers are ATP-hydrolyzing machines specialized to restructure, mobilize or eject nucleosomes, allowing regulated exposure of DNA in chromatin. Recently, remodelers have been analyzed using single-molecule techniques in real time, revealing them to be complex DNA-pumping machines. The results both support and challenge aspects of current models of remodeling, supporting the idea that the remodeler translocates or pumps DNA loops into and around the nucleosome, while also challenging earlier concepts about loop formation, the character of the loop and how it propagates. Several complex behaviors were observed, such as reverse translocation and long translocation bursts of the remodeler, without appreciable DNA twist. This review presents and discusses revised models for nucleosome sliding and ejection that integrate this new information with the earlier biochemical studies.Many processes involving chromosomes are guided by DNA-binding proteins, and the access of these proteins to DNA is regulated by chromatin. Nucleosomes, the primary repeating unit of chromatin, package DNA by wrapping 147 base pairs (bp) around an octamer of histone proteins in ∼1.7 helical turns 1-3 . This packaging provides topological order but occludes one face of the DNA, which slows or prevents the recognition of DNA sequences by DNA-binding proteins. To maintain topological order, and also to allow rapid and regulated access to the DNA, cells have evolved a set of chromatin-remodeling machines that alter nucleosome position, presence and structure.Remodelers can be separated into several families on the basis of their composition and activities: SWI/SNF, ISWI, NURD/Mi-2/CHD and the 'split ATPases' INO80 and SWR1 (which bear an insertion within their ATPase domains). Rad54 may represent an additional family, as it perturbs chromatin in vitro, but it apparently lacks specific nucleosome-interacting domains 4,5 . The participation of remodelers in various chromosomal processes has been the subject of many reviews 6-9 . The present work focuses solely on remodeler mechanisms, and primarily on the function of their conserved catalytic subunit, a superfamily 2 (SF2) ATPdependent DNA translocase. Recently, single-molecule approaches have been used to examine several remodelers, providing many new insights into their behavior. Here I discuss these recent studies, compare them with previous biochemical studies and suggest refinements to existing models to account for some of the observations. Remodelers slide, eject and restructure nucleosomesRemodelers can affect nucleosomes in at least four ways ( Fig. 1): (i) sliding, or moving the histone octamer to a new position, which exposes DNA 10-12 ; (ii) ejection, or completely displacing the octamer to expose DNA [13][14][15][16] ; (iii) removal of H2A-H2B dimers, leaving only the central H3-H4 tetramer, which exposes DNA and destabilizes the nucleosome 17,18 ; and (iv) dimer replacement-for example, exchanging the resident H2A-H2B dimers for dimers NIH Public Access

show abstract

“…Second, it has been shown that transcriptionally active chromatin is depleted in (H2A-H2B) dimers (11); and this has later been confirmed for RNA polymerase II in vitro (12). Third, recent results indicate that chromatin remodeling at the promoter of the Pho5 gene involves the complete transient loss of histones (13).…”

mentioning

confidence: 91%

A New Fluorescence Resonance Energy Transfer Approach Demonstrates That the Histone Variant H2AZ Stabilizes the Histone Octamer within the Nucleosome

Park

Dyer

Tremethick

et al. 2004

Journal of Biological Chemistry

202

200

View full text Add to dashboard Cite

Nucleosomes are highly dynamic macromolecular complexes that are assembled and disassembled in a modular fashion. One important way in which this dynamic process can be modulated is by the replacement of major histones with their variants, thereby affecting nucleosome structure and function. Here we use fluorescence resonance energy transfer between fluorophores attached to various defined locations within the nucleosome to dissect and compare the structural transitions of a H2A.Z containing and a canonical nucleosome in response to increasing ionic strength. We show that the peripheral regions of the DNA dissociate from the surface of the histone octamer at relatively low ionic strength, under conditions where the dimer-tetramer interaction remains unaffected. At around 550 mM NaCl, the (H2A-H2B) dimer dissociates from the (H3-H4) 2 tetramer-DNA complex. Significantly, this latter transition is stabilized in nucleosomes that have been reconstituted with the essential histone variant H2A.Z. Our studies firmly establish fluorescence resonance energy transfer as a valid method to study nucleosome stability, and shed new light on the biological function of H2A.Z.Chromatin is built from nucleosomes, the universally repeating protein-DNA complexes in all eukaryotic cells. The crystal structure of the nucleosome core particle (NCP) 1 (1) reveals an octameric histone core around which 147 base pairs of DNA are wrapped in 1.65 tight superhelical turns. The histone octamer itself is a modular assembly of two copies each of the four histone proteins H2A, H2B, H3, and H4. Two histone pairs, composed either of H2A and H2B, or H3 and H4, form stable heterodimers. In solution, two H3-H4 dimers form a tetramer in the shape of a flat, twisted horseshoe that binds the central 60 base pairs of the nucleosomal DNA around its outside (1, 2). One (H2A-H2B) dimer is tethered to each face of the (H3-H4) 2 tetramer-DNA complex, to complete a "helical ramp" for continued DNA binding (reviewed in Ref.3).The interaction between the two histone subcomplexes occurs via two spatially distinct interaction interfaces of quite different character (Fig. 1). A four-helix bundle structure (formed by H2B and H4) is characterized mainly by hydrophobic interactions, and buries 1000 Å 2 (1). The second, larger interface (1600 Å 2 ) is characterized mostly by direct and solvent-mediated hydrogen bonds between the "docking domain" of H2A, and the histone fold extensions of H3 and H4 (4). In addition, a small interface is formed between the L1 loops of the two H2A molecules, which may contribute to holding together the two gyres of the DNA superhelix at the back of the nucleosome (Fig. 1) (5). Under physiological conditions, the (H2A-H2B) dimer associates stably with the (H3-H4) 2 tetramer only in the presence of DNA (6). Each (H2A-H2B) dimer organizes 30 base pairs toward either end of the DNA. The penultimate 10 base pairs of nucleosomal DNA on either side are organized by a region of H3 that does not form an integral part of the (H3-H4) 2 tetramer, an...

show abstract

Histones Are First Hyperacetylated and Then Lose Contact with the Activated PHO5 Promoter

Cited by 374 publications

References 43 publications

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

Chromatin remodeling: insights and intrigue from single-molecule studies

A New Fluorescence Resonance Energy Transfer Approach Demonstrates That the Histone Variant H2AZ Stabilizes the Histone Octamer within the Nucleosome

Contact Info

Product

Resources

About