HMG1 and 2, and related ‘architectural’ DNA-binding proteins

Thomas, Jean O.; Travers, Andrew

doi:10.1016/s0968-0004(01)01801-1

Cited by 585 publications

(596 citation statements)

References 66 publications

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“…For the DNAbending proteins studied here, the role of helix-opening cooperativity is not clear since they induce only local disruptions of DNA secondary structure. However, it has been observed that distorted DNA structures are favored HMGB and HU protein binding sites (1,3,14,42), and it would be of interest to carry out experiments along the lines of those presented here to study how distorted DNA substrates affect binding stability.…”

Section: Discussionmentioning

confidence: 99%

Micromechanical Analysis of the Binding of DNA-Bending Proteins HMGB1, NHP6A, and HU Reveals Their Ability To Form Highly Stable DNA−Protein Complexes

et al. 2004

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The mechanical response generated by binding of the nonspecific DNA-bending proteins HMGB1, NHP6A, and HU to single tethered 48.5 kb λ-DNA molecules is investigated using DNA micromanipulation. As protein concentration is increased, the force needed to extend the DNA molecule increases, due to its compaction by protein-generated bending. Most significantly, we find that for each of HMGB1, NHP6A, and HU there is a well-defined protein concentration, not far above the binding threshold, above which the proteins do not spontaneously dissociate. In this regime, the amount of protein bound to the DNA, as assayed by the degree to which the DNA is compacted, is unperturbed either by replacing the surrounding protein solution with protein-free buffer or by straightening of the molecule by applied force. Thus, the stability of the protein-DNA complexes formed is dependent on the protein concentration during the binding. HU is distinguished by a switch to a DNA-stiffening function at the protein concentration where the formation of highly stable complexes occurs. Finally, introduction of competitor DNA fragments into the surrounding solution disassembles the stable DNA complexes with HMGB1, NHP6A, and HU within seconds. Since spontaneous dissociation of protein does not occur on a time scale of hours, we conclude that this rapid protein exchange in the presence of competitor DNA must occur only via "direct" DNA-DNA contact. We therefore observe that protein transport along DNA by direct transfers occurs even for proteins such as NHP6A and HU that have only one DNA-binding domain.Non-histone DNA-bending proteins are associated with chromosomes of prokaryotic and eukaryotic cells. Prominent among these in eukaryotes are the nonspecifically binding class of HMGB 1 proteins, present in the nucleus at micromolar concentrations (1-3). HMGB proteins possess a ∼75 amino acid residue DNA-minor-groove-binding domain, which induces a bend of about 90°. Charged residues within extended peptide segments at the N-or C-termini of the HMGB domain can strongly modulate DNA binding affinities of these proteins. Saccharomyces cereVisiae NHP6A contains one HMGB domain but binds DNA with considerably higher affinity than mammalian HMGB1, which contains two domains (4). HMGB proteins function in a variety of localized DNA transactions including assembly of transcription and recombination complexes and chromatin remodeling (1-3). A general role for HMGB proteins in modulating global DNA organization in eukaryotes is not yet established, but yeast HMGB proteins have been shown to condense chromosomal DNA in prokaryotic models (4,5).

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Section: Discussionmentioning

confidence: 99%

Micromechanical Analysis of the Binding of DNA-Bending Proteins HMGB1, NHP6A, and HU Reveals Their Ability To Form Highly Stable DNA−Protein Complexes

et al. 2004

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“…However, in principle, proteins that constrain negative superhelicity might be expected to bind preferentially to DNA within a narrow range of superhelical density, as has been shown for the FIS protein, which favors a low negative superhelical density (Schneider et al 1997). There is unfortunately little information available for other proteins, but another possible example would be the eukaryotic HMG domain, which, in addition to being the principal component of the small HMGB proteins (Thomas and Travers 2001), is found in certain subunits of chromatin remodeling complexes (Quinn et al 1996) and of transcription elongation complexes (Orphanides et al 1999;Brewster et al 2001;Formosa et al 2001;Mason and Struhl 2003). The small HMGB proteins themselves may also play an essential role in these processes (Moreira and Holmberg 2000).…”

Section: Gradients Of Superhelicity and Protein Bindingmentioning

confidence: 99%

“…Although negative superhelicity can promote transient strand separation in particular sequences , it is only one of several mechanisms that may potentially create short stretches of DNA lacking continuous base pairing. Both HU and the HMGB proteins also bind with high affinity to, for example, Holliday junctions, DNA bulges and cis-platin-modified DNA (Balandina et al 2002;Thomas and Travers 2001;Malarkey and Churchill 2012). Many studies of HMG domain-containing proteins have emphasized their ability to bend DNA by ∼90° (Jamieson et al 1999;Lorenz et al 1999).…”

Section: Gradients Of Superhelicity and Protein Bindingmentioning

confidence: 99%

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

Muskhelishvili

Travers

2016

Biophys Rev

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We argue that dynamic changes in DNA supercoiling in vivo determine both how DNA is packaged and how it is accessed for transcription and for other manipulations such as recombination. In both bacteria and eukaryotes, the principal generators of DNA superhelicity are DNA translocases, supplemented in bacteria by DNA gyrase. By generating gradients of superhelicity upstream and downstream of their site of activity, translocases enable the differential binding of proteins which preferentially interact with respectively more untwisted or more writhed DNA. Such preferences enable, in principle, the sequential binding of different classes of protein and so constitute an essential driver of chromatin organization.Keywords DNA supercoiling . DNA translocases . Chromatin organization . Superhelicity gradients . DNA untwisting . DNAwrithing Dynamic changes of DNA supercoiling act as a driving force behind the alterations of genetic activity and DNA compaction both in eukaryotes and prokaryotes. Both these processes involve formation of spatially organized nucleoprotein structures by DNA architectural proteins. Whereas in eukaryotes the paradigmal example is the histone octamer, in prokaryotes a similar function is attributed to a small class of highly abundant nucleoid-associated proteins. We argue that, depending on the primary sequence organization, the changes of superhelicity elicit various alterations of local DNA geometry, while these, in turn, facilitate the assembly of distinct nucleoprotein structures pertinent to genetic function. Genome-wide conversion of the superhelical energy into various three-dimensional DNA structures thus acts as an analogue code coordinating the energy supply with the genetic expression of the chromosome.Recent studies make it increasingly clear that the DNA double helix carries at least two types of encoded information and that these include the well-known genetic code and the structural information determining the form and physical properties of the double helix itself. Since both these information types are inscribed in the same DNA sequence, and yet one is discrete whereas the other is continuous, they have been respectively dubbed the digital and analog DNA codes (Marr et al. 2008;Travers et al. 2012;Muskhelishvili and Travers 2013). The potential of the DNA to adopt distinct configurations is strongly modulated by DNA supercoiling, which is increasingly recognized as one of the major forces coordinating the cellular DNA transactions in both prokaryotes (including Archaea) and eukaryotes.DNA supercoiling can be generated by the simple application of torque to the double helix (Strick et al. 1998) but, importantly, because the DNA molecule itself possesses chirality-it is, after all, a right-handed double helix-the local structures stabilized by changes in superhelical density depend on both the sign and strength of the applied torque. For example, both positive and negative torque (respectively overand underwinding of the double helix) can change the intrinsic coiling of ...

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“…Maintenance, establishment, and modification of global chromatin organization and local chromatin structure are modulated by a large number of chromatin-binding proteins that generate transcriptionally permissive or repressed chromatin domains in response to environmental stimuli (Workman and Kingston, 1998;Peterson and Workman, 2000;Jones and Kadonaga, 2000;Wu and Grunstein, 2000;Wolffe and Hansen, 2001;Becker et al, 2002). The association of linker histones and nonhistone and heterochromatin-specific proteins such as high mobility group proteins and HP1 play key roles in the generation of higher order chromatin structures (Arents et al, 1991; Luger et al, 1997;Bustin, 1999;Eissenberg and Elgin, 2000;Hill, 2001;Thomas and Travers, 2001;Woodcock and Dimitrov, 2001;Grewal and Elgin, 2002;Bianchi and Agresti, 2005;Bustin et al, 2005;Verschure et al, 2005). The stearically restricted environment presented by chromatin is in part overcome by multisubunit protein complexes that enzymatically regulate chromatin structure.…”

Section: Introductionmentioning

confidence: 99%

Chromatin Remodeling Complexes Interact Dynamically with a Glucocorticoid Receptor–regulated Promoter

Johnson

Elbi

Parekh

et al. 2008

MBoC

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Brahma (BRM) and Brahma-related gene 1 (BRG1) are the ATP-dependent catalytic subunits of the SWI/SNF family of chromatin-remodeling complexes. These complexes are involved in essential processes such as cell cycle, growth, differentiation, and cancer. Using imaging approaches in a cell line that harbors tandem repeats of stably integrated copies of the steroid responsive MMTV-LTR (mouse mammary tumor virus-long terminal repeat), we show that BRG1 and BRM are recruited to the MMTV promoter in a hormone-dependent manner. The recruitment of BRG1 and BRM resulted in chromatin remodeling and decondensation of the MMTV repeat as demonstrated by an increase in the restriction enzyme accessibility and in the size of DNA fluorescence in situ hybridization (FISH) signals. This chromatin remodeling event was concomitant with an increased occupancy of RNA polymerase II and transcriptional activation at the MMTV promoter. The expression of ATPase-deficient forms of BRG1 (BRG1-K-R) or BRM (BRM-K-R) inhibited the remodeling of local and higher order MMTV chromatin structure and resulted in the attenuation of transcription. In vivo photobleaching experiments provided direct evidence that BRG1, BRG1-K-R, and BRM chromatin-remodeling complexes have distinct kinetic properties on the MMTV array, and they dynamically associate with and dissociate from MMTV chromatin in a manner dependent on hormone and a functional ATPase domain. Our data provide a kinetic and mechanistic basis for the BRG1 and BRM chromatin-remodeling complexes in regulating gene expression at a steroid hormone inducible promoter. INTRODUCTIONThe eukaryotic genome is organized into higher order chromatin structures in the nucleus. The regulation of eukaryotic gene expression in the context of chromatin is a complex event and is essential for numerous cellular processes (Lemon and Tjian, 2000;Orphanides and Reinberg, 2002;Labrador and Corces, 2002;Maniatis and Reed, 2002;Felsenfeld and Groudine, 2003;Roberts and Orkin, 2004). Maintenance, establishment, and modification of global chromatin organization and local chromatin structure are modulated by a large number of chromatin-binding proteins that generate transcriptionally permissive or repressed chromatin domains in response to environmental stimuli (Workman and Kingston, 1998;Peterson and Workman, 2000;Jones and Kadonaga, 2000;Wu and Grunstein, 2000;Wolffe and Hansen, 2001;Becker et al., 2002). The association of linker histones and nonhistone and heterochromatin-specific proteins such as high mobility group proteins and HP1 play key roles in the generation of higher order chromatin structures (Arents et al., 1991; Luger et al., 1997;Bustin, 1999;Eissenberg and Elgin, 2000;Hill, 2001;Thomas and Travers, 2001;Woodcock and Dimitrov, 2001;Grewal and Elgin, 2002;Bianchi and Agresti, 2005;Bustin et al., 2005;Verschure et al., 2005). The stearically restricted environment presented by chromatin is in part overcome by multisubunit protein complexes that enzymatically regulate chromatin structure. These complexes can e...

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HMG1 and 2, and related ‘architectural’ DNA-binding proteins

Cited by 585 publications

References 66 publications

Micromechanical Analysis of the Binding of DNA-Bending Proteins HMGB1, NHP6A, and HU Reveals Their Ability To Form Highly Stable DNA−Protein Complexes

Micromechanical Analysis of the Binding of DNA-Bending Proteins HMGB1, NHP6A, and HU Reveals Their Ability To Form Highly Stable DNA−Protein Complexes

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

Chromatin Remodeling Complexes Interact Dynamically with a Glucocorticoid Receptor–regulated Promoter

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