SWI/SNF chromatin remodeling complex is critical for the expression of microphthalmia-associated transcription factor in melanoma cells

2010 ◽  
Vol 392 (3) ◽  
pp. 454-459 ◽  
Author(s):  
Jiri Vachtenheim ◽  
Lubica Ondrušová ◽  
Jan Borovanský
2010 ◽  
Vol 344 (1) ◽  
pp. 489-490
Author(s):  
Scott J. Nowak ◽  
Hitoshi Aihara ◽  
Katie Gonzalez ◽  
Yutaka Nibu ◽  
Mary K. Baylies

Author(s):  
Nadia Habel ◽  
Najla El-Hachem ◽  
Frédéric Soysouvanh ◽  
Hanene Hadhiri-Bzioueche ◽  
Serena Giuliano ◽  
...  

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.


2012 ◽  
Vol 287 (40) ◽  
pp. 33567-33580 ◽  
Author(s):  
Mariana Herrera-Cruz ◽  
Grisel Cruz ◽  
Viviana Valadez-Graham ◽  
Mariana Fregoso-Lomas ◽  
Claudia Villicaña ◽  
...  

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Jianfeng Lin ◽  
Youbao Zhao ◽  
Aileen R. Ferraro ◽  
Ence Yang ◽  
Zachary A. Lewis ◽  
...  

AbstractCellular differentiation is instructed by developmental regulators in coordination with chromatin remodeling complexes. Much information about their coordination comes from studies in the model ascomycetous yeasts. It is not clear, however, what kind of information that can be extrapolated to species of other phyla in Kingdom Fungi. In the basidiomycete Cryptococcus neoformans, the transcription factor Znf2 controls yeast-to-hypha differentiation. Through a forward genetic screen, we identified the basidiomycete-specific factor Brf1. We discovered Brf1 works together with Snf5 in the SWI/SNF chromatin remodeling complex in concert with existent Znf2 to execute cellular differentiation. We demonstrated that SWI/SNF assists Znf2 in opening the promoter regions of hyphal specific genes, including the ZNF2 gene itself. This complex also supports Znf2 to fully associate with its target regions. Importantly, our findings revealed key differences in composition and biological function of the SWI/SNF complex in the two major phyla of Kingdom Fungi.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Timo H. Lüdtke ◽  
Irina Wojahn ◽  
Marc-Jens Kleppa ◽  
Jasper Schierstaedt ◽  
Vincent M. Christoffels ◽  
...  

Abstract Background Tbx2 encodes a transcriptional repressor implicated in the development of numerous organs in mouse. During lung development TBX2 maintains the proliferation of mesenchymal progenitors, and hence, epithelial proliferation and branching morphogenesis. The pro-proliferative function was traced to direct repression of the cell-cycle inhibitor genes Cdkn1a and Cdkn1b, as well as of genes encoding WNT antagonists, Frzb and Shisa3, to increase pro-proliferative WNT signaling. Despite these important molecular insights, we still lack knowledge of the DNA occupancy of TBX2 in the genome, and of the protein interaction partners involved in transcriptional repression of target genes. Methods We used chromatin immunoprecipitation (ChIP)-sequencing and expression analyses to identify genomic DNA-binding sites and transcription units directly regulated by TBX2 in the developing lung. Moreover, we purified TBX2 containing protein complexes from embryonic lung tissue and identified potential interaction partners by subsequent liquid chromatography/mass spectrometry. The interaction with candidate proteins was validated by immunofluorescence, proximity ligation and individual co-immunoprecipitation analyses. Results We identified Il33 and Ccn4 as additional direct target genes of TBX2 in the pulmonary mesenchyme. Analyzing TBX2 occupancy data unveiled the enrichment of five consensus sequences, three of which match T-box binding elements. The remaining two correspond to a high mobility group (HMG)-box and a homeobox consensus sequence motif. We found and validated binding of TBX2 to the HMG-box transcription factor HMGB2 and the homeobox transcription factor PBX1, to the heterochromatin protein CBX3, and to various members of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex including HDAC1, HDAC2 and CHD4. Conclusion Our data suggest that TBX2 interacts with homeobox and HMG-box transcription factors as well as with the NuRD chromatin remodeling complex to repress transcription of anti-proliferative genes in the pulmonary mesenchyme.


Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 520
Author(s):  
Wenfeng Nie ◽  
Jinyu Wang

As essential structural components of ATP-dependent chromatin-remodeling complex, the nucleolus-localized actin-related proteins (ARPs) play critical roles in many biological processes. Among them, ARP4 is identified as an integral subunit of chromatin remodeling complex SWR1, which is conserved in yeast, humans and plants. It was shown that RNAi mediated knock-down of Arabidopsis thaliana ARP4 (AtARP4) could affect plant development, specifically, leading to early flowering. However, so far, little is known about how ARP4 functions in the SWR1 complex in plant. Here, we identified a loss-of-function mutant of AtARP4 with a single nucleotide change from glycine to arginine, which had significantly smaller leaf size. The results from the split luciferase complementation imaging (LCI) and yeast two hybrid (Y2H) assays confirmed its physical interaction with the scaffold and catalytic subunit of SWR1 complex, photoperiod-independent early flowering 1 (PIE1). Furthermore, mutation of AtARP4 caused altered transcription response of hundreds of genes, in which the number of up-regulated differentially expressed genes (DEGs) was much larger than those down-regulated. Although most DEGs in atarp4 are related to plant defense and response to hormones such as salicylic acid, overall, it has less overlapping with other swr1 mutants and the hta9 hta11 double-mutant. In conclusion, our results reveal that AtARP4 is important for plant growth and such an effect is likely attributed to its repression on gene expression, typically at defense-related loci, thus providing some evidence for the coordination of plant growth and defense, while the regulatory patterns and mechanisms are distinctive from other SWR1 complex components.


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