scholarly journals FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells

2021 ◽  
Author(s):  
Nadia Habel ◽  
Najla El-Hachem ◽  
Frédéric Soysouvanh ◽  
Hanene Hadhiri-Bzioueche ◽  
Serena Giuliano ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Target Gene ◽  
Tumor Development ◽  
Melanoma Cells ◽  
Complex Activity ◽  
Cellular Processes ◽  
Chromatin Remodeling Complex ◽  
Chromatin Remodeling Complexes ◽  
Proliferation And Invasion

AbstractUbiquitination by serving as a major degradation signal of proteins, but also by controlling protein functioning and localization, plays critical roles in most key cellular processes. Here, we show that MITF, the master transcription factor in melanocytes, controls ubiquitination in melanoma cells. We identified FBXO32, a component of the SCF E3 ligase complex as a new MITF target gene. FBXO32 favors melanoma cell migration, proliferation, and tumor development in vivo. Transcriptomic analysis shows that FBXO32 knockdown induces a global change in melanoma gene expression profile. These include the inhibition of CDK6 in agreement with an inhibition of cell proliferation and invasion upon FBXO32 silencing. Furthermore, proteomic analysis identifies SMARC4, a component of the chromatin remodeling complexes BAF/PBAF, as a FBXO32 partner. FBXO32 and SMARCA4 co-localize at loci regulated by FBXO32, such as CDK6 suggesting that FBXO32 controls transcription through the regulation of chromatin remodeling complex activity. FBXO32 and SMARCA4 are the components of a molecular cascade, linking MITF to epigenetics, in melanoma cells.

scholarly journals In Vivo Silencing of Genes Coding for dTip60 Chromatin Remodeling Complex Subunits Affects Polytene Chromosome Organization and Proper Development in Drosophila melanogaster

2021 ◽  
Vol 22 (9) ◽  
pp. 4525
Author(s):  
Yuri Prozzillo ◽  
Stefano Cuticone ◽  
Diego Ferreri ◽  
Gaia Fattorini ◽  
Giovanni Messina ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Chromatin Remodeling ◽  
Cell Biology ◽  
Reverse Genetics ◽  
Developmentally Regulated ◽  
Chromatin Remodeling Complex ◽  
Chromatin Remodeling Complexes ◽  
Histone Modifying Enzymes ◽  
Classical Genetics

Chromatin organization is developmentally regulated by epigenetic changes mediated by histone-modifying enzymes and chromatin remodeling complexes. In Drosophila melanogaster, the Tip60 chromatin remodeling complex (dTip60) play roles in chromatin regulation, which are shared by evolutionarily-related complexes identified in animal and plants. Recently, it was found that most subunits previously assigned to the dTip60 complex are shared by two related complexes, DOM-A.C and DOM-B.C, defined by DOM-A and DOM-B isoforms, respectively. In this work, we combined classical genetics, cell biology, and reverse genetics approaches to further investigate the biological roles played during Drosophila melanogaster development by a number of subunits originally assigned to the dTip60 complex.

scholarly journals Yeast Isw1p Forms Two Separable Complexes In Vivo

2003 ◽  
Vol 23 (1) ◽  
pp. 80-91 ◽  
Author(s):  
Jay C. Vary, ◽  
Vamsi K. Gangaraju ◽  
Jun Qin ◽  
Carolyn Church Landel ◽  
Charles Kooperberg ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcriptional Regulation ◽  
Chromatin Remodeling ◽  
Elevated Temperatures ◽  
Cellular Processes ◽  
Biochemical Assays ◽  
Associated Proteins ◽  
Chromatin Remodeling Complexes ◽  
Specific Activities

ABSTRACT There are several classes of ATP-dependent chromatin remodeling complexes, which modulate the structure of chromatin to regulate a variety of cellular processes. The budding yeast, Saccharomyces cerevisiae, encodes two ATPases of the ISWI class, Isw1p and Isw2p. Previously Isw1p was shown to copurify with three other proteins. Here we identify these associated proteins and show that Isw1p forms two separable complexes in vivo (designated Isw1a and Isw1b). Biochemical assays revealed that while both have equivalent nucleosome-stimulated ATPase activities, Isw1a and Isw1b differ in their abilities to bind to DNA and nucleosomal substrates, which possibly accounts for differences in specific activities in nucleosomal spacing and sliding. In vivo, the two Isw1 complexes have overlapping functions in transcriptional regulation of some genes yet distinct functions at others. In addition, these complexes show different contributions to cell growth at elevated temperatures.

Aryl Hydrocarbon Receptor: Its Regulation and Roles in Transformation and Tumorigenesis

2019 ◽  
Vol 20 (6) ◽  
pp. 625-634 ◽  
Author(s):  
Xun Che ◽  
Wei Dai
Keyword(s):  
Target Gene ◽  
Tumor Development ◽  
Environmental Response ◽  
Carcinogenic Effect ◽  
Post Translational Modifications ◽  
Downstream Target ◽  
Aryl Hydrocarbon ◽  
Downstream Target Gene ◽  
Major Mediator

AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.

scholarly journals An In Vitro System Recapitulates Chromatin Remodeling at the PHO5 Promoter

1999 ◽  
Vol 19 (4) ◽  
pp. 2817-2827 ◽  
Author(s):  
Elizabeth S. Haswell ◽  
Erin K. O’Shea
Keyword(s):  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Nuclear Extract ◽  
In Vitro System ◽  
Chromatin Remodeling Complex ◽  
Promoter Dna ◽  
Pho5 Promoter

ABSTRACT The Saccharomyces cerevisiae gene PHO5 is an excellent system with which to study regulated changes in chromatin structure. The PHO5 promoter is packaged into four positioned nucleosomes under repressing conditions; upon induction, the structure of these nucleosomes is altered such that the promoter DNA becomes accessible to nucleases. We report here the development and characterization of an in vitro system in which partially purified PHO5 minichromosomes undergo promoter chromatin remodeling. Several hallmarks of thePHO5 chromatin transition in vivo were reproduced in this system. Chromatin remodeling of PHO5minichromosomes required the transcription factors Pho4 and Pho2, was localized to the promoter region of PHO5, and was independent of the chromatin-remodeling complex Swi-Snf. In vitro chromatin remodeling also required the addition of fractionated nuclear extract and hydrolyzable ATP. This in vitro system should serve as a useful tool for identifying the components required for this reaction and for elucidating the mechanism by which the PHO5promoter chromatin structure is changed.

scholarly journals Interaction of Papillomavirus E2 Protein with the Brm Chromatin Remodeling Complex Leads to Enhanced Transcriptional Activation

2006 ◽  
Vol 81 (5) ◽  
pp. 2213-2220 ◽  
Author(s):  
R. Ajay Kumar ◽  
Samisubbu R. Naidu ◽  
Xiaoyu Wang ◽  
Anthony N. Imbalzano ◽  
Elliot J. Androphy
Keyword(s):  
Chromatin Remodeling ◽  
Transcriptional Activation ◽  
Potential Interaction ◽  
Transactivation Domain ◽  
Reporter System ◽  
Barr Virus ◽  
Amino Terminal ◽  
Chromatin Remodeling Complex ◽  
Epstein Barr

ABSTRACT Papillomavirus E2 is a sequence-specific DNA binding protein that regulates transcription and replication of the viral genome. The transcriptional activities of E2 are typically evaluated by transient transfection of nonreplicating E2-dependent reporters. We sought to address whether E2 activates transcription in an episomal context and its potential interaction with the chromatin remodeling proteins. Using an Epstein-Barr virus-based episomal reporter, we demonstrate that E2 stimulates transcription from an E2-dependent promoter in a chromatin context. This activation is enhanced by the presence of proteins associated with SWI/SNF complexes, which are ATP-dependent chromatin remodeling enzymes. We show that exogenous expression of the Brm ATPase enhances E2 activity in SWI/SNF-deficient cell lines and that the amino-terminal transactivation domain of E2 mediates association with the Brm complex in vivo. Using chromatin immunoprecipitation assays, we demonstrate that Brm enhances promoter occupancy by E2 in an episomal context. Our results demonstrate that E2 activates transcription from an episomal reporter system and reveal a novel property of E2 in collaborating with the Brm chromatin remodeling complex in enhancing transcriptional activation.

scholarly journals Cryo-electron microscopy structure of a nucleosome-bound SWI/SNF chromatin remodeling complex

2019 ◽  
Author(s):  
Yan Han ◽  
Alexis A Reyes ◽  
Sara Malik ◽  
Yuan He
Keyword(s):  
Electron Microscopy ◽  
Chromatin Remodeling ◽  
Atp Hydrolysis ◽  
Protein Complexes ◽  
Gene Activation ◽  
The Body ◽  
Cellular Processes ◽  
Cryo Electron Microscopy ◽  
Chromatin Remodeling Complex ◽  
High Resolution Structure

AbstractThe multi-subunit chromatin remodeling complex SWI/SNF1–3 is highly conserved from yeast to humans and plays critical roles in various cellular processes including transcription and DNA damage repair4, 5. It uses the energy from ATP hydrolysis to remodel chromatin structure by sliding and evicting the histone octamer6–10, creating DNA regions that become accessible to other essential protein complexes. However, our mechanistic understanding of the chromatin remodeling activity is largely hindered by the lack of a high-resolution structure of any complex from this family. Here we report the first structure of SWI/SNF from the yeast S. cerevisiae bound to a nucleosome at near atomic resolution determined by cryo-electron microscopy (cryo-EM). In the structure, the Arp module is sandwiched between the ATPase and the Body module of the complex, with the Snf2 HSA domain connecting all modules. The HSA domain also extends into the Body and anchors at the opposite side of the complex. The Body contains an assembly scaffold composed of conserved subunits Snf12 (SMARCD/BAF60), Snf5 (SMARCB1/BAF47/ INI1) and an asymmetric dimer of Swi3 (SMARCC/BAF155/170). Another conserved subunit Swi1 (ARID1/BAF250) folds into an Armadillo (ARM) repeat domain that resides in the core of the SWI/SNF Body, acting as a molecular hub. In addition to the interaction between Snf2 and the nucleosome, we also observed interactions between the conserved Snf5 subunit and the histones at the acidic patch, which could serve as an anchor point during active DNA translocation. Our structure allows us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and propose a model of how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation11–13.

scholarly journals The Role of BRG1 in Antioxidant and Redox Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Shilong You ◽  
Ying Zhang ◽  
Jiaqi Xu ◽  
Hao Qian ◽  
Shaojun Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chromatin Remodeling ◽  
Redox Homeostasis ◽  
Redox Signaling ◽  
Normal Functioning ◽  
Antioxidant Genes ◽  
Cellular Processes ◽  
Cell Functions ◽  
Chromatin Remodeling Complex

Redox homeostasis is regulated by critical molecules that modulate antioxidant and redox signaling (ARS) within the cell. Imbalances among these molecules can lead to oxidative stress and damage to cell functions, causing a variety of diseases. Brahma-related gene 1 (BRG1), also known as SMARCA4, is the central ATPase catalytic subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, which plays a core role in DNA replication, repair, recombination, and transcriptional regulation. Numerous recent studies show that BRG1 is involved in the regulation of various cellular processes associated with ARS. BRG1, as a major factor in chromatin remodeling, is essential for the repair of oxidative stress-induced DNA damage and the activation of antioxidant genes under oxidative stress. Consequently, a comprehensive understanding of the roles of BRG1 in redox homeostasis is crucial to understand the normal functioning as well as pathological mechanisms. In this review, we summarized and discussed the role of BRG1 in the regulation of ARS.

scholarly journals Structure of theArabidopsisTOPLESS corepressor provides insight into the evolution of transcriptional repression

2017 ◽  
Vol 114 (30) ◽  
pp. 8107-8112 ◽  
Author(s):  
Raquel Martin-Arevalillo ◽  
Max H. Nanao ◽  
Antoine Larrieu ◽  
Thomas Vinos-Poyo ◽  
David Mast ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Transcriptional Repression ◽  
Site Directed Mutagenesis ◽  
Crystallographic Structure ◽  
Hormone Signaling ◽  
Chromatin Remodeling Complexes ◽  
Insight Into ◽  
Similar Domain

Transcriptional repression involves a class of proteins called corepressors that link transcription factors to chromatin remodeling complexes. In plants such asArabidopsis thaliana, the most prominent corepressor is TOPLESS (TPL), which plays a key role in hormone signaling and development. Here we present the crystallographic structure of theArabidopsisTPL N-terminal region comprising the LisH and CTLH (C-terminal to LisH) domains and a newly identified third region, which corresponds to a CRA domain. Comparing the structure of TPL with the mammalian TBL1, which shares a similar domain structure and performs a parallel corepressor function, revealed that the plant TPLs have evolved a new tetramerization interface and unique and highly conserved surface for interaction with repressors. Using site-directed mutagenesis, we validated those surfaces in vitro and in vivo and showed that TPL tetramerization and repressor binding are interdependent. Our results illustrate how evolution used a common set of protein domains to create a diversity of corepressors, achieving similar properties with different molecular solutions.

The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3955-3966 ◽  
Author(s):  
O. Papoulas ◽  
S.J. Beek ◽  
S.L. Moseley ◽  
C.M. McCallum ◽  
M. Sarte ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Protein Complexes ◽  
Dominant Negative ◽  
Homeotic Genes ◽  
Atpase Subunit ◽  
Trithorax Group ◽  
Chromatin Remodeling Complexes ◽  
Trithorax Group Proteins ◽  
Drosophila Embryos

The trithorax group gene brahma (brm) encodes an activator of Drosophila homeotic genes that functions as the ATPase subunit of a large protein complex. To determine if BRM physically interacts with other trithorax group proteins, we purified the BRM complex from Drosophila embryos and analyzed its subunit composition. The BRM complex contains at least seven major polypeptides. Surprisingly, the majority of the subunits of the BRM complex are not encoded by trithorax group genes. Furthermore, a screen for enhancers of a dominant-negative brm mutation identified only one trithorax group gene, moira (mor), that appears to be essential for brm function in vivo. Four of the subunits of the BRM complex are related to subunits of the yeast chromatin remodeling complexes SWI/SNF and RSC. The BRM complex is even more highly related to the human BRG1 and hBRM complexes, but lacks the subunit heterogeneity characteristic of these complexes. We present biochemical evidence for the existence of two additional complexes containing trithorax group proteins: a 2 MDa ASH1 complex and a 500 kDa ASH2 complex. These findings suggest that BRM plays a role in chromatin remodeling that is distinct from the function of most other trithorax group proteins.

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