GFI1 tethers the nucleosome-remodeling and histone-deacetylase (NuRD) complex to open and transcriptionally active chromatin in myeloid progenitors
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ABSTRACT:
PROVIDER: PRJNA725908 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: The goals of this study are to identify sites in genomic DNA that are occupied by GFI1 and the NurD complex, represented by its member the chromodomain helicase CHD4 or by a complex of GFI1 and CHD4 in myeloid precursors cells and to determined the effect on gene expression. Methods: Granulocytic-monocytic precursors (GMPs) as well as pre neutrophils and mature neutrophils were sorted by flow cytometry from murine bone marrow and sujected to RNA-seq and Chromatin-immuno-precipitation and sequencing (ChIP-Seq) and ATAC-seq procedures. Ch-IP seq experiments were done with antibodies against GFI1, CHD4 or different histone H3 modifications as indicated. Results: GFI1 and GFI1/CHD4 complexes occupies both promoter and enhancers of genes that are down or upregulated during the formation of preNeu and matNeu cells from GMPs Conclusions: Myeloid precursors required GFI1 to tether the NuRD complex to a specific set of target genes that are either transcriptionally active or poised to enable their transcriptional regulation during neutrophil differentiation by chromatin remodeling
2021-10-13 | GSE173533 | GEO
Project description:GFI is a DNA binding transcriptional repressor that regulates myeloid differentiation. Here, we show that GFI1 interacts with the chromodomain helicase CHD4 and other components of the nucleosome remodeling and deacetylase (NuRD) complex. Our data demonstrated that GFI1 and GFI1/CHD4 complexes occupy sites of open chromatin enriched for histone marks associated with active transcription or different sets of genes that are either enriched for IRF1 or SPI-1 consensus binding sites. In addition, our study provided evidence that GFI1 affects the chromatin remodeling activity of the NuRD complex. Overall, our results indicate that GFI1/CHD4 complexes control chromatin openness and histone modifications differentially to regulate target genes, which govern the immune response, nucleosome organization, or metabolic processes.
2021-11-02 | PXD028945 | Pride
Project description:The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for development in complex animals but has been refractory to detailed analysis because of its low abundance and resistance to recombinant production. As part of a larger project, absolute quantification using isotopically-labelled AQUA peptides was performed on natively-purified NuRD and six recombinantly-expressed NuRD subcomplexes. This is the first time the NuRD complex has been quantified using the AQUA strategy.
2021-01-08 | PXD010110 | Pride
Project description:The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for development in complex animals but has been refractory to detailed analysis because of its low abundance and resistance to recombinant production. In combination with other techniques, crosslinking mass spectrometry was used to elucidate the structure of the Nucleosome Remodelling and Deacetylase (NuRD) complex. Natively-purified NuRD, and four recombinantly-expressed NuRD subcomplexes, and a PWWP2A-MTA-HDAC-RBBP alternative ‘NuRD-like’ complex were subjected to crosslinking with DSS, ADH, BS3 and DMTMM.
2021-01-08 | PXD010111 | Pride
Project description:The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for normal development in metazoans and has direct implications in a range of human diseases. Amongst all classes of chromatin remodeling complexes, the NuRD complex has been the most recalcitrant to analysis. This is, in part, due to difficulties with producing the intact complex recombinantly. Using affinity-purification followed by mass spectrometry, we determined the stoichiometry of the NuRD complex from three cancer cell lines representing three different human tissues. We also analysed the data to determine the interactome of the NuRD complex and identified potential NuRD interactors.
2019-03-13 | PXD012061 | Pride
Project description:Pluripotency and self-renewal, the defining properties of embryonic stem cells, are brought about by transcriptional programs involving an intricate network of transcription factors and chromatin remodelling complexes. The Nucleosome Remodelling and Deacetylase (NuRD) complex plays a crucial and dynamic role in the regulation of stemness and differentiation. Several NuRD-associated factors have been reported but how they are organised has not been investigated in detail. Here, we have combined affinity purification and blue native polyacrylamide gel electrophoresis followed by protein identification by mass spectrometry and protein correlation profiling to characterise the topology of the NuRD complex. Our data show that in mouse embryonic stem cells the NuRD complex is present as two distinct assemblies of differing topology with different binding partners. Cell cycle regulator Cdk2ap1 and transcription factor Sall4 associate only with the higher mass NuRD assembly. We further establish that only isoform Sall4A, and not Sall4B, associates with NuRD. By contrast, Suz12, a component of the PRC2 Polycomb repressor complex, associates with the lower mass entity. In addition, we identify and validate a novel NuRD-associated protein, Wdr5, a regulatory subunit of the MLL histone methyltransferase complex, which associates with both NuRD entities. Bioinformatic analyses of published target gene sets of these chromatin binding proteins are in agreement with these structural observations. In summary, this study provides an interesting insight into mechanistic aspects of NuRD function in stem cell biology. The relevance of our work has broader implications because of the ubiquitous nature of the NuRD complex. The strategy described here can be more broadly applicable to investigate the topology of the multiple complexes an individual protein can participate in.
2016-01-05 | PXD002452 | Pride
Project description:Growth factor indepdendent 1 (GFI1) is a SNAG-domain, DNA binding transcriptional repressor which controls myeloid differentiation through molecular mechanisms and co-factors that still remain to be clearly identified. Here we show that GFI1 associates with the chromodomain helicase DNA binding protein 4 (CHD4) and other components of the Nucleosome remodeling and deacetylase (NuRD) complex. In granulo-monocytic precursors, GFI1, CHD4 or GFI1/CHD4 complexes occupy sites enriched for histone marks associated with active transcription suggesting that GFI1 recruits the NuRD complex to target genes regulated by active or bivalent promoters and enhancers. GFI1 and GFI1/CHD4 complexes occupy promoters that are either enriched for IRF1 or SPI1 consensus binding sites, respectively. During neutrophil differentiation, chromatin closure and depletion of H3K4me2 occurs at different degrees depending on whether GFI1, CHD4 or both are present, indicating that GFI1 is more efficient in depleting of H3K4me2 and -me1 marks when associated with CHD4. Our data suggest that GFI1/CHD4 complexes regulate histone modifications differentially to enable regulation of target genes affecting immune response, nucleosome organization or cellular metabolic processes and that both the target gene specificity and the activity of GFI1 during myeloid differentiation depends on the presence of chromatin remodeling complexes.
| S-EPMC8639993 | biostudies-literature
Project description:Mitochondrial stress during development causes widespread changes in chromatin structure to promote mitochondrial unfolded protein response (UPRmt), perpetuating an early response across a lifetime results in lifespan extension. We found that the nucleosome remodeling and deacetylase (NuRD) complex interact with the transcription factor DVE-1 to initiate the global chromatin condensation and induce the UPRmt in animals experienced with mild mitochondrial dysfunction. The condensed chromatin structure can be well maintained into later life that is beneficial for lifespan extension. Moreover, overexpression of the core component of the NuRD complex is sufficient to induce the UPRmt response and longevity in C. elegans. Thus, a transient mitochondrial stress response during early development is established and propagated into later life through the NuRD-dependent chromatin remodeling pathway to extend lifespan.
2020-07-31 | GSE143904 | GEO
Project description:Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2u Nucleosome Remodeling and Deacetylase (NuRD) complex is controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethers this complex to active lymphoid differentiation genes, but keeps it in a functionally-poised state. Loss in Ikaros DNA binding activity causes a local increase in Mi-2u chromatin remodeling, histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributes to transcriptionally-poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their re-activation. Thus release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally-opposing epigenetic mechanisms and genetic networks. We used microarrays to detail the global programme of gene expression of mouse DP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage. 8 samples (mouse DP thymocytes from wt, and different stage after Ikaros inactivation) are analyzed Mouse Microarray Expression platforms, Affymetrix Mouse 430 2.0. Examination of different histone modifications and binding sites for Ikaros, Mi2beta in wild type DP thymocytes, and Ikaros knockout thymocytes.
2011-11-13 | E-GEOD-32311 | biostudies-arrayexpress
Project description:Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2u Nucleosome Remodeling and Deacetylase (NuRD) complex is controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethers this complex to active lymphoid differentiation genes, but keeps it in a functionally-poised state. Loss in Ikaros DNA binding activity causes a local increase in Mi-2u chromatin remodeling, histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributes to transcriptionally-poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their re-activation. Thus release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally-opposing epigenetic mechanisms and genetic networks. We used microarrays to detail the global programme of gene expression of mouse DP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage.
2011-11-13 | GSE32311 | GEO