Exchange of histones H1, H2A, and H2B in vivo

Louters, Larry L.; Chalkley, Roger

doi:10.1021/bi00334a002

Cited by 99 publications

(74 citation statements)

References 31 publications

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“…In a related study, we used this technique to demonstrate that transcription factor binding near the nucleosomal dyad results in transient dissociation of the DNA ends. 3 The observed dissociation of the (H2A-H2B) dimer at relatively low ionic strength is consistent with in vivo observations (9,10,44).…”

Section: Discussionsupporting

confidence: 84%

“…For example, the ends of the bound nucleosomal DNA are thought to dissociate and re-associate with the histone core in a rapid equilibrium, to allow access of factors to nucleosomal DNA (49). The (H2A-H2B) dimer can exchange dynamically in interphase nuclei, independent of replication-dependent chromatin assembly pathways (9,10). The replacement of histone H2A with histone variants would be a simple and efficient way to alter the thermodynamic properties of the nucleosome, and thus change the local and global structure of chromatin (for example, see Ref.…”

Section: Discussionmentioning

confidence: 99%

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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

203

200

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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...

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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

203

200

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“…We first confirmed that H2AX is poly-and monoubiquitinated after the induction of DSBs by UV irradiation of bromodeoxyuridinelabeled cells (data not shown). We then performed photobleaching analysis to assess histone binding properties in vivo following the induction of DSBs with the laser UVA microirradiation system (20,24,27). We confirmed that the stably expressed GFP-H2AX proteins in HeLa and GM02063 cells share a range of physiological properties with the endogenous histone: GFP-H2AX was found to localize in chromatin throughout the cell cycle, similar to other histones, and the salt extraction profile was similar to that of the endogenous H2AX (data not shown) (44).…”

Section: Vol 27 2007 Release Of H2ax In Dna Damage Response 7033mentioning

confidence: 99%

DNA Damage-Dependent Acetylation and Ubiquitination of H2AX Enhances Chromatin Dynamics

Ikura

Tashiro

Kakino

et al. 2007

Molecular and Cellular Biology

343

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Chromatin reorganization plays an important role in DNA repair, apoptosis, and cell cycle checkpoints. Among proteins involved in chromatin reorganization, TIP60 histone acetyltransferase has been shown to play a role in DNA repair and apoptosis. However, how TIP60 regulates chromatin reorganization in the response of human cells to DNA damage is largely unknown. Here, we show that ionizing irradiation induces TIP60 acetylation of histone H2AX, a variant form of H2A known to be phosphorylated following DNA damage. Furthermore, TIP60 regulates the ubiquitination of H2AX via the ubiquitin-conjugating enzyme UBC13, which is induced by DNA damage. This ubiquitination of H2AX requires its prior acetylation. We also demonstrate that acetylation-dependent ubiquitination by the TIP60-UBC13 complex leads to the release of H2AX from damaged chromatin. We conclude that the sequential acetylation and ubiquitination of H2AX by TIP60-UBC13 promote enhanced histone dynamics, which in turn stimulate a DNA damage response.Chromatin reorganization by histone modification and mobilization plays a crucial role in DNA metabolism, including replication, transcription, and repair. It appears that histone modification and mobilization can reorganize chromatin to allow DNA repair machinery to access damaged chromosomal DNA (11,29,52,56,57).H2AX is a histone variant that differs from H2A at various amino acid residues along the entire protein and in its Cterminal extensions. H2AX is phosphorylated after the induction of DNA double-strand breaks (DSBs), and the phosphorylated H2AX (␥-H2AX) participates in focus formation at sites of DNA damage. After induction of DSBs, the MRN complex (MRE11, RAD50, and NBS1) binds to broken DNA ends and recruits active ATM, ATR, and/or DNA protein kinase, resulting in the initial phosphorylation of H2AX (32,38,40). MDC1 then associates with ␥-H2AX and recruits additional activated ATM to the sites of DSBs (23,46). This positive feedback loop leads to the expansion of the ␥-H2AX region surrounding DSBs and provides docking sites for many DNA damage and repair proteins, including the MRN complex, 53BP1, and BRCA1 (5, 6, 46). ␥-H2AX plays a role in the accumulation but not in the initial recruitment of repair factors such as the MRN complex, 53BP1, and BRCA1 (10, 63). Therefore, modifications of H2AX other than phosphorylation could play a role in the initial step of the DNA damage response.Until recently, the biological significance of ubiquitination in the DNA damage response has been unclear. H2B ubiquitination regulates the damage checkpoint response (15). H2A is ubiquitinated during the response to UV-induced DNA damage (8). UV-induced DNA damage also causes the ubiquitination of histones H3 and H4, resulting in their release from chromatin (60). Interestingly, ubiquitin-conjugated proteins appear to be accumulated at sites of DSBs, forming nuclear foci like ␥-H2AX (34). These findings raise the possibility that histone ubiquitination is also involved in the reorganization of chromatin in response to D...

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“…The lability of the interaction between H2A-H2B dimers and (H3-H4) 2 tetramers may have a significance for the nucleosome-conformational changes observed in cells. Indeed, actively transcribing chromatin is depleted in H2A-H2B dimers (3) that are rapidly exchanged (21,26). Factors such as nucleoplasmin or NAP1 interact with H2A-H2B dimers and stimulate the binding of regulatory factors to their cognate DNA targets assembled in chromatin via, most probably, removal of the H2A-H2B dimers (7,50).…”

mentioning

confidence: 99%

Role of Histone N-Terminal Tails and Their Acetylation in Nucleosome Dynamics

Morales¹,

Richard-Foy²

2000

Molecular and Cellular Biology

101

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Histone N-terminal tails are central to the processes that modulate nucleosome structure and function. We have studied the contribution of core histone tails to the structure of a single nucleosome and to a histone (H3-H4) 2 tetrameric particle assembled on a topologically constrained DNA minicircle. The effect of histone tail cleavage and histone tail acetylation on the structure of the nucleoprotein particle was investigated by analyzing the DNA topoisomer equilibrium after relaxation of DNA torsional stress by topoisomerase I. Removal of the H3 and H4 N-terminal tails, as well as their acetylation, provoked a dramatic change in the linking-number difference of the (H3-H4) 2 tetrameric particle, with a release of up to 70% of the negative supercoiling previously constrained by this structure. The (H3-H4) 2 tetramers containing tailless or hyperacetylated histones showed a striking preference for relaxed DNA over negatively supercoiled DNA. This argues in favor of a change in tetramer structure that constrains less DNA and adopts a relaxed flat conformation instead of its left-handed conformation within the nucleosome. In contrast neither removal or hyperacetylation of H3 and H4 tails nor removal or hyperacetylation of H2A and H2B N-terminal tails affected the nucleosome structure. This indicates that the globular domain of H2A and H2B is sufficient to stabilize the tailless or the hyperacetylated (H3-H4) 2 tetramer in a left-handed superhelix conformation. These results suggest that the effect of histone tail acetylation that facilitates transcription may be mediated via transient formation of an (H3-H4) 2 tetrameric particle that could adopt an open structure only when H3 and/or H4 tails are hyperacetylated.

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Exchange of histones H1, H2A, and H2B in vivo

Cited by 99 publications

References 31 publications

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

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

DNA Damage-Dependent Acetylation and Ubiquitination of H2AX Enhances Chromatin Dynamics

Role of Histone N-Terminal Tails and Their Acetylation in Nucleosome Dynamics

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