HMGB proteins and gene expression

Agresti, A; Bianchi, Marco E.

doi:10.1016/s0959-437x(03)00023-6

Cited by 349 publications

(326 citation statements)

References 48 publications

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“…Our EMSA data showed that HMGB2 does not directly bind to regulatory DNA elements but it augments DNA binding of Lef-1. HMGB2 does not alter the electrophoretic mobility of Lef-1 complexed with oligonucleotides, suggesting that HMGB2 dissociates from the complex after having provided its architectural activity (42). Similar results were observed for HMGB1, which increased the affinity of p53 complexes with oligonucleotides (43).…”

Section: Discussionsupporting

confidence: 69%

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

Taniguchi

Caramés

Kawakami

et al. 2009

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

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The superficial zone (SZ) of articular cartilage is critical in maintaining tissue function and homeostasis and represents the site of the earliest changes in osteoarthritis. Mechanisms that regulate the unique phenotype of SZ chondrocytes and maintain SZ integrity are unknown. We recently demonstrated that expression of the chromatin protein high mobility group box (HMGB) protein 2 is restricted to the SZ in articular cartilage suggesting a transcriptional regulation involving HMGB2 in SZ. Here, we show that an interaction between HMGB2 and the Wnt/␤-catenin pathway regulates the maintenance of the SZ. We found that the Wnt/␤-catenin pathway is active specifically in the SZ in normal mouse knee joints and colocalizes with HMGB2. Both Wnt signaling and HMGB2 expression decrease with aging in mouse joints. Our molecular studies show that HMGB2 enhances the binding of Lef-1 to its target sequence and potentiates transcriptional activation of the Lef-1-␤-catenin complex. The HMG domain within HMGB2 is crucial for interaction with Lef-1, suggesting that both HMGB2 and HMGB1 may be involved in this function. Furthermore, conditional deletion of ␤-catenin in cultured mouse chondrocytes induced apoptosis. These findings define a pathway where protein interactions of HMGB2 and Lef-1 enhance Wnt signaling and promote SZ chondrocyte survival. Loss of the HMGB2-Wnt signaling interaction is a new mechanism in aging-related cartilage pathology.aging ͉ osteoarthritis ͉ apoptosis ͉ superficial zone A rticular cartilage is a tissue that provides biomechanical properties that allow near frictionless joint movement and dispersion of mechanical loads. Cartilage is composed of a single cell lineage but differences in the organization, phenotype and function of cells in the various layers of cartilage have been recognized (1-4). The superficial zone (SZ) is the most unique. SZ cells produce lubricin, also termed proteoglycan-4 (PRG4) or superficial zone protein (SZP), an important joint lubricant (5-7), and are more responsive to stimulation by catabolic cytokines such as IL-1 (8). Recent studies also suggest that the SZ contains cells that express mesenchymal stem cell markers (9-11).Articular cartilage is among the tissues that undergo profound aging-related changes and aging represents the major risk factor for osteoarthritis (OA), the most prevalent joint disease (12). Agingrelated changes in cartilage include reduced cellularity, increased apoptosis and altered cellular responses to growth factors, cytokines and mechanical stress (13-15). Cartilage changes in aging and OA begin in the SZ and once the SZ is disrupted this is followed by progressive erosion of the remaining cartilage layers (16).To address mechanisms that maintain the unique phenotype of SZ cells we performed gene expression analyses and observed that expression of the chromatin protein HMGB2 is restricted to the SZ (17). Joint aging in humans and mice leads to loss of HMGB2 expression and this is correlated with the onset of OA-like changes. Mice deficient in Hm...

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Section: Discussionsupporting

confidence: 69%

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

Taniguchi

Caramés

Kawakami

et al. 2009

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

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“…Because the HMGB box family does not bind to DNA in a sequence-specific manner, PyHMGB2 is likely to be recruited to DNA by other factors or by a specific chromatin context (17). Interestingly, yeast two-hybrid interaction data (36) show that HMGB2 is in the center of a broader network of proteins potentially involved in transcription regulation, including three AP2 domain plant-like transcription factors (supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…HMGB box proteins are small transcriptional regulators that bind DNA in a nonsequence-specific fashion and bend it, leading to the recruitment of RNA polymerase II and the induction of transcription (17). HMGB proteins also actively participate in chromatin remodeling by increasing nucleosome sliding and accessibility of the chromatin (17). The two Plasmodium falciparum HMGB proteins, HMGB1 (PFL0145c) and HMGB2 (MAL8P1.72), have the biochemical characteristics of the HMGB box family of transcriptional regulators (16).…”

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confidence: 99%

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High Mobility Group Protein HMGB2 Is a Critical Regulator of Plasmodium Oocyst Development

Gissot

Ting

Daly

et al. 2008

Journal of Biological Chemistry

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The sexual cycle of Plasmodium is required for transmission of malaria from mosquitoes to mammals, but how parasites induce the expression of genes required for the sexual stages is not known. We disrupted the Plasmodium yoelii gene encoding high mobility group nuclear factor hmgb2, which encodes a DNA-binding protein potentially implicated in transcriptional regulation of malaria gene expression. We investigated its function in vivo in the vertebrate and invertebrate hosts. ⌬pyhmgb2 parasites develop into gametocytes but have drastic impairment of oocyst formation. A global transcriptome analysis of the ⌬pyhmgb2 parasites identified ϳ30 genes whose expression is down-regulated in the ⌬pyhmgb2 parasites. These genes are conserved in all malaria species, and more than 90% of these genes show a peak of mRNA expression at the gametocyte stage. Surprisingly, the transcripts coding for the Plasmodium berghei orthologues of those genes are stored and translated in the ookinete stage. Therefore, sexual stage protein expression appears to be both transcriptionally and translationally regulated with Plasmodium HMGB2 acting as an important regulator of malaria sexual stage gene expression.Plasmodium species, the causative agents of malaria, are the most deadly members of the apicomplexan phylum. As with other members of the Apicomplexa, Plasmodium has a multifaceted life cycle encompassing an asexual phase within the intermediate host and a sexual cycle in the mosquito. Gametocytogenesis and gametogenesis consist of an ensemble of processes leading to the differentiation of erythrocytic forms of the parasite into male or female gametocytes. These complex and coordinated steps ensure the transmission of the parasite to the invertebrate host and are required for transmission of malaria to mammalian hosts. Gametocytes form in mammalian host, are taken up by the mosquito during a blood meal, transform into gametes in the mosquito midgut, and then fuse to form a zygote. Zygotes differentiate into ookinetes that penetrate the midgut wall and differentiate into oocysts, in which sporozoites will develop.Starting from the well controlled vertebrate milieu, the parasite must adapt to the mosquito environment where temperature fluctuates and nutrients are limited. Gametocytogenesis requires growth arrest and a differentiation step that will prepare the parasite for these changes. Sexual differentiation is accompanied by a tightly controlled gene expression program during which ϳ200 -300 mRNAs are specifically expressed or predominantly expressed in sexual forms of the parasite (1-4). Transcriptional control of gene expression is implicated as a crucial step during this process with sex-specific transcript expression in gametocytes controlled by the sequences in the 5Ј-flanking regions (5).For some sexual stage genes post-translational processes mediate gene expression. The genes coding for P25 and P28 ookinete proteins (PY00522 and PY00523, respectively) are transcribed at the gametocyte stage, but their translation is delayed unti...

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“…[47][48][49][50][51] The angle of this bend has been reported to fall somewhere in the 308 to 1308 range, although values between 708 and 908 are typical for a domain with a single HMG box. 49,[52][53][54][55] HMGB proteins are thought to enable the binding of transcription factors, 50,51,[56][57][58][59] either by binding directly to the factors 60,61 or by stabilizing DNA looping. 62 HMGB proteins have been observed to aid the formation of DNA loop complexes, similarly to the role of HU.…”

Section: Protein Binding To the Double Helixmentioning

confidence: 99%

Mechanisms of DNA binding determined in optical tweezers experiments

McCauley¹,

Williams²

2006

Biopolymers

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The last decade has seen rapid development in single molecule manipulation of RNA and DNA. Measuring the response force for a particular manipulation has allowed the free energies of various nucleic acid structures and configurations to be determined. Optical tweezers represent a class of single molecule experiments that allows the energies and structural dynamics of DNA to be probed up to and beyond the transition from the double helix to its melted single strands. These experiments are capable of high force resolution over a wide dynamic range. Additionally, these investigations may be compared with results obtained when the nucleic acids are in the presence of proteins or other binding ligands. These ligands may bind into the major or minor groove of the double helix, intercalate between bases or associate with an already melted single strand of DNA. By varying solution conditions and the pulling dynamics, energetic and dynamic information may be deduced about the mechanisms of binding to nucleic acids, providing insight into the function of proteins and the utility of drug treatments. © 2006 Wiley Periodicals, Inc. Biopolymers 85:154–168, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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HMGB proteins and gene expression

Cited by 349 publications

References 48 publications

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

High Mobility Group Protein HMGB2 Is a Critical Regulator of Plasmodium Oocyst Development

Mechanisms of DNA binding determined in optical tweezers experiments

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