The p150 subunit of the histone chaperone Caf-1 interacts with the transcriptional repressor Gfi1

Heyd, Florian; Chen, Riyan; Afshar, Khashayar; Saba, Ingrid; Lazure, Claude; Fiolka, Katharina; Möröy, Tarik

doi:10.1016/j.bbagrm.2011.04.009

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…These protein associations were reported previously with the FL Chaf1a, and we confirmed their interactions with the T1 construct in transfected Plat-E cells ( Fig. 5B; Heyd et al 2011;Yang et al 2015). These data suggest that the KER region is required for the interaction of Chaf1a with these epigenetic modifiers.…”

Section: Characterization Of Chaf1a Domains Involved In Cd4 Silencingsupporting

confidence: 91%

“…Chaf1a associates with histone-modifying enzymes that are also required for the maintenance of Cd4 silencing CAF-1 is reported to contribute to the maintenance of heterochromatin integrity through its association with factors and enzymatic activities enriched at heterochromatin loci (Reese et al 2003;Sarraf and Stancheva 2004;Heyd et al 2011;Yang et al 2015;Cheloufi and Hochedlinger 2017). Using the rescue and dominant-negative constructs T1 and T10, respectively, we screened for binding partners by mass spectrometry in transfected Plat-E cells.…”

Section: Characterization Of Chaf1a Domains Involved In Cd4 Silencingmentioning

confidence: 99%

“…CAF-1 is a conserved heterotrimeric complex comprised of Chaf1a, Chaf1b, and Rbbp4 that promotes H3-H4 deposition during DNA replication in S phase (Smith and Stillman 1989;Kaufman et al 1995). The CAF-1 complex has well-established roles in the maintenance of heterochromatin and cell identity, but its function in regulating gene expression in primary somatic cells and its coordination with DNA methylation in gene silencing have been largely unexplored (Tchenio et al 2001;Krawitz et al 2002;Houlard et al 2006;Dohke et al 2008;Quivy et al 2008;Huang et al 2010;Heyd et al 2011;Cheloufi et al 2015;Ishiuchi et al 2015;Roelens et al 2017). Mechanistically, we found that the CAF-1 subunit Chaf1a associates with the histone deacetylases (HDACs) HDAC1/2 and the histone demethylase LSD1, enzymes that counteract histone marks associated with active transcription.…”

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confidence: 99%

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The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells

Aichinger

Nguyen

et al. 2019

Genes Dev.

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The transcriptional repression of alternative lineage genes is critical for cell fate commitment. Mechanisms by which locus-specific gene silencing is initiated and heritably maintained during cell division are not clearly understood. To study the maintenance of silent gene states, we investigated how the Cd4 gene is stably repressed in CD8 + T cells. Through CRISPR and shRNA screening, we identified the histone chaperone CAF-1 as a critical component for Cd4 repression. We found that the large subunit of CAF-1, Chaf1a, requires the N-terminal KER domain to associate with the histone deacetylases HDAC1/2 and the histone demethylase LSD1, enzymes that also participate in Cd4 silencing. When CAF-1 was lacking, Cd4 derepression was markedly enhanced in the absence of the de novo DNA methyltransferase Dnmt3a but not the maintenance DNA methyltransferase Dnmt1. In contrast to Dnmt1, Dnmt3a deficiency did not significantly alter levels of DNA methylation at the Cd4 locus. Instead, Dnmt3a deficiency sensitized CD8 + T cells to Cd4 derepression mediated by compromised functions of histonemodifying factors, including the enzymes associated with CAF-1. Thus, we propose that the heritable silencing of the Cd4 gene in CD8 + T cells exploits cooperative functions among the DNA methyltransferases, CAF-1, and histone-modifying enzymes.

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Section: Characterization Of Chaf1a Domains Involved In Cd4 Silencingsupporting

confidence: 91%

Section: Characterization Of Chaf1a Domains Involved In Cd4 Silencingmentioning

confidence: 99%

mentioning

confidence: 99%

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The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells

Aichinger

Nguyen

et al. 2019

Genes Dev.

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“…Among these are RTT106, and the protein complex CAF‐1 (chromatin assembly factor 1). Current models predict a role for CAF‐1 mostly in replication‐dependent chromatin assembly (Kaufman et al ., 1997; Takami et al ., 2007), although recent reports indicate an additional role in transcription (Kim et al ., 2009; Heyd et al ., 2011). RTT106, similar to ASF1, is implicated both in replication‐dependent and in replication‐independent processes (Huang et al ., 2005; Kim et al ., 2007; Mousson et al ., 2007; Takahata et al ., 2009; Silva et al ., 2012).…”

Section: Resultsmentioning

confidence: 99%

The histone chaperone ASF1 is essential for sexual development in the filamentous fungus Sordaria macrospora

Gesing¹,

Schindler²,

Fränzel

et al. 2012

Molecular Microbiology

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SummaryAscomycetes develop four major types of fruiting bodies that share a common ancestor, and a set of common core genes most likely controls this process. One way to identify such genes is to search for conserved expression patterns. We analysed microarray data of Fusarium graminearum and Sordaria macrospora, identifying 78 genes with similar expression patterns during fruiting body development. One of these genes was asf1 (anti-silencing function 1), encoding a predicted histone chaperone. asf1 expression is also upregulated during development in the distantly related ascomycete Pyronema confluens. To test whether asf1 plays a role in fungal development, we generated an S. macrospora asf1 deletion mutant. The mutant is sterile and can be complemented to fertility by transformation with the wild-type asf1 and its P. confluens homologue. An ASF1-EGFP fusion protein localizes to the nucleus. By tandem-affinity purification/mass spectrometry as well as yeast twohybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners. Several developmental genes are dependent on asf1 for correct transcriptional expression. Deletion of the histone chaperone genes rtt106 and cac2 did not cause any developmental phenotypes. These data indicate that asf1 of S. macrospora encodes a conserved histone chaperone that is required for fruiting body development.

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“…Growth factor independence 1 (GFI1) was first reported to have important roles in Interluekin‐2 independence T cell lymphoma growth (Gilks, Bear, Grimes, & Tsichlis, ). As a transcriptional repressor, GFI1 represses the target gene transcription and is required for hematopoiesis (Fiolka et al, ) and immune cell differentiation (Karsunky et al, ; Kazanjian, Gross, & Grimes, ) by recruiting histone deacetylases, de‐methylases, or methyltransferases (Duan, Zarebski, Montoya‐Durango, Grimes, & Horwitz, ; Heyd et al, ; McGhee et al, ; Montoya‐Durango et al, ; Zweidler‐Mckay, Grimes, Flubacher, & Tsichlis, ). The functional loss of Gfi1 causes various hematologic diseases, such as severe congenital neutropenia in human and mouse (Geissler et al, ; Phelan, Shroyer, Cook, Gebelein, & Grimes, ).…”

Section: Introductionmentioning

confidence: 99%

Gfi1‐GCE inducible Cre line for hair cell‐specific gene manipulation in mouse inner ear

Tang

et al. 2019

Genesis

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Tissue-specific inducible Cre recombinase mouse lines allow precise genetic manipulations in spatiotemporal manners and are pivotal for functional studies of genes during development and in adults. Growth factor independence 1 (GFI1) is an essential transcription factor expressed in the hair cells of mouse inner ear and Gfi1 locus serves as an excellent anchor site to drive the expression of inducible Cre recombinase in mouse inner hair cells. In this study, we have generated Gfi1-P2A-GFP-CreERT2 (Gfi1-GCE) knock-in mouse line by in-frame fusion of a selfcleaving GCE to the C-terminus of GFI1. We have shown that as predicted, the expression of GCE and GFI1 was detected specifically in the cytosol and nuclei of hair cells, respectively, of uninduced Gfi1-GCE mice, suggesting the successful cleavage and simultaneous expression of GFI1 and GCE. In addition, the in-frame fusion of the self-cleaving GCE does not interrupt the function of Gfi1 in the inner ear. Administration of tamoxifen leads to nuclear translocation of GCE and results in an efficient activation of tdTomato reporter gene expression specifically in most hair cells throughout development and in adults. Thus, this inducible Gfi1-GCE mouse line is a highly efficient Cre deleter and is suitable for gene manipulation in developing and adult inner ear hair cells.

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The p150 subunit of the histone chaperone Caf-1 interacts with the transcriptional repressor Gfi1

Cited by 9 publications

References 31 publications

The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells

The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells

The histone chaperone ASF1 is essential for sexual development in the filamentous fungus Sordaria macrospora

Gfi1‐GCE inducible Cre line for hair cell‐specific gene manipulation in mouse inner ear

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