SETDB1 Regulate Cell State Maintenance and Cell Fate Differentiation in DG
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PROVIDER: PRJNA1242744 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we explored the function of histone methyltransferase SETDB1 in the development of the mouse dentate gyrus (DG). We discovered that a critical role of Setdb1 in steering the early development path of DG NSCs towards adult neural stem cells and astrocytes destinies. In an effort to delineate the exact molecular mechanisms of aberrant postnatal NSCs and astrocytes caused by Setdb1-deleted NSCs, we utilized a suite of techniques including RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) and Setdb1-Flag Cleavage Under Targets and Tagmentation (CUT&Tag) in both wild-type (WT) and Setdb1-deficient DG samples. Combination of transcriptome and epigenome analysis indicate that COX6B2 as a key target of SETDB1 for regulating maintenance of early postnatal NSCs and differentiation of astrocytes. Taken together, our results highlight the importance of transcriptomic and chromatin landscapes for metabolic reprogramming and identify a exquisite mechanism underlyling the cell state maintenance and cell fate differentiation.
2025-08-06 | GSE293069 | GEO
Project description:In this study, we explored the function of histone methyltransferase SETDB1 in the development of the mouse dentate gyrus (DG). We discovered that a critical role of Setdb1 in steering the early development path of DG NSCs towards adult neural stem cells and astrocytes destinies. In an effort to delineate the exact molecular mechanisms of aberrant postnatal NSCs and astrocytes caused by Setdb1-deleted NSCs, we utilized a suite of techniques including RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) and Setdb1-Flag Cleavage Under Targets and Tagmentation (CUT&Tag) in both wild-type (WT) and Setdb1-deficient DG samples. Combination of transcriptome and epigenome analysis indicate that COX6B2 as a key target of SETDB1 for regulating maintenance of early postnatal NSCs and differentiation of astrocytes. Taken together, our results highlight the importance of transcriptomic and chromatin landscapes for metabolic reprogramming and identify a exquisite mechanism underlyling the cell state maintenance and cell fate differentiation.
2025-08-06 | GSE270622 | GEO
Project description:SETDB1 Orchestrates Metabolic Reprogramming to Regulate Cell State Maintenance and Cell Fate Differentiation
| PRJNA1127580 | ENA
Project description:Transcription factors that play key roles in regulating embryonic stem (ES) cell state have been identified, but the chromatin regulators that help maintain ES cells are less well understood. A high-throughput shRNA screen was used to identify novel chromatin regulators that influence ES cell state. Loss of histone H3K9 methyltransferases, particularly SetDB1, had the most profound effects on ES cells. ChIP-Seq and functional analysis revealed that SetDB1 and histone H3K9 methylated nucleosomes occupy and repress genes encoding developmental regulators. These SetDB1-occupied genes are a subset of the M-bM-^@M-^\bivalentM-bM-^@M-^] genes, which contain nucleosomes with H3K4me3 and H3K27me3 modifications catalyzed by trithorax and polycomb group proteins, respectively. These genes are subjected to repression by both polycomb group proteins and SetDB1, and loss of either regulator can destabilize ES cell state. ChIP-seq data for SetDB1 and H3K9me3 in mouse ES cells.
2009-11-01 | E-GEOD-18371 | biostudies-arrayexpress
Project description:F-actin dynamics regulates mammalian organ growth and cell fate maintenance
| PRJNA480812 | ENA
Project description:Transcription factors that play key roles in regulating embryonic stem (ES) cell state have been identified, but the chromatin regulators that help maintain ES cells are less well understood. A high-throughput shRNA screen was used to identify novel chromatin regulators that influence ES cell state. Loss of histone H3K9 methyltransferases, particularly SetDB1, had the most profound effects on ES cells. ChIP-Seq and functional analysis revealed that SetDB1 and histone H3K9 methylated nucleosomes occupy and repress genes encoding developmental regulators. These SetDB1-occupied genes are a subset of the “bivalent” genes, which contain nucleosomes with H3K4me3 and H3K27me3 modifications catalyzed by trithorax and polycomb group proteins, respectively. These genes are subjected to repression by both polycomb group proteins and SetDB1, and loss of either regulator can destabilize ES cell state.
2009-11-01 | GSE18371 | GEO
Project description:Only a small percentage of human transcription factors (e.g. those associated with a specific differentiation program) are expressed in a given cell type. Thus, cell fate is mainly determined by cell type-specific silencing of transcription factors that drive different cellular lineages. Several histone modifications have been associated with gene silencing, including H3K27me3 and H3K9me3. We have previously shown that the two largest classes of mammalian transcription factors are marked by distinct histone modifications; homeobox genes are marked by H3K27me3 and zinc finger genes are marked by H3K9me3. Several histone methyltransferases (e.g. G9a and SETDB1) may be involved in mediating the H3K9me3 silencing mark. We have used ChIP-chip (GSE24480) and ChIP-seq to demonstrate that SETDB1, but not G9a, is associated with regions of the genome enriched for H3K9me3. A current model is that SETDB1 is recruited to specific genomic locations via interaction with the corepressor TRIM28 (KAP1), which is in turn recruited to the genome via interaction with zinc finger transcription factors that contain a Kruppel-associated box (KRAB) domain. However, specific KRAB-ZNFs that recruit TRIM28 (KAP1) and SETDB1 to the genome have not been identified. We now show that ZNF274 (a KRAB-ZNF that contains 5 C2H2 zinc finger domains), can interact with KAP1 in vitro and, using ChIP-seq, we show that ZNF274 binding sites co-localize with SETDB1, KAP1, and H3K9me3 at the 3’ ends of zinc finger genes. Knockdown of ZNF274 with siRNAs reduced the levels of KAP1 and SETDB1 recruitment to the binding sites. These studies provide the first identification of a KRAB domain-containing ZNFs that is involved in recruitment of the KAP1 and SETDB1 to the human genome. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf 7 total ChIP-seq datasets; 4 ZNF274 datasets done in duplicate from 4 different cell lines; 1 KAP1 duplicate dataset done in duplicate from K562 cells; 1 SetDB1 duplicate dataset from K562 cells; 1 H3K9me3 duplicate dataset from K562 cells
2010-11-15 | E-GEOD-24632 | biostudies-arrayexpress
Project description:Only a small percentage of human transcription factors (e.g. those associated with a specific differentiation program) are expressed in a given cell type. Thus, cell fate is mainly determined by cell type-specific silencing of transcription factors that drive different cellular lineages. Several histone modifications have been associated with gene silencing, including H3K27me3 and H3K9me3. We have previously shown that the two largest classes of mammalian transcription factors are marked by distinct histone modifications; homeobox genes are marked by H3K27me3 and zinc finger genes are marked by H3K9me3. Several histone methyltransferases (e.g. G9a and SETDB1) may be involved in mediating the H3K9me3 silencing mark. We have used ChIP-chip and ChIP-seq (GSE24632) to demonstrate that SETDB1, but not G9a, is associated with regions of the genome enriched for H3K9me3. A current model is that SETDB1 is recruited to specific genomic locations via interaction with the corepressor TRIM28 (KAP1), which is in turn recruited to the genome via interaction with zinc finger transcription factors that contain a Kruppel-associated box (KRAB) domain. However, specific KRAB-ZNFs that recruit TRIM28 (KAP1) and SETDB1 to the genome have not been identified. We now show that ZNF274 (a KRAB-ZNF that contains 5 C2H2 zinc finger domains), can interact with KAP1 in vitro and, using ChIP-seq, we show that ZNF274 binding sites co-localize with SETDB1, KAP1, and H3K9me3 at the 3â ends of zinc finger genes. Knockdown of ZNF274 with siRNAs reduced the levels of KAP1 and SETDB1 recruitment to the binding sites. These studies provide the first identification of a KRAB domain-containing ZNFs that is involved in recruitment of the KAP1 and SETDB1 to the human genome. This study includes the 4 ChIP-chip arrays only.
2010-11-01 | E-GEOD-24480 | biostudies-arrayexpress
Project description:transcription profiles of two groups each containing 5 strains of Disseminated gonorrhoeae (DG) and Undisseminated (superficial) gonorrhoeae (UG) were compared. An additional set of comparisons was done between 4 strains from group one Disseminated gonorrhoeae (DG) and another 4 strains from the same group.
2012-06-15 | E-MEXP-3254 | biostudies-arrayexpress
Project description:Griffin GK, Wu J, Iracheta-Vellve A, Patti JC, Hsu J, Davis T, Dele-Oni D, Du PP, Halawi A, Ishizuka JJ, Kim S, Klaeger S, Knudsen NH, Miller BC, Nguyen T, Olander K, Papanastasiou M, Rachimi S, Robitschek EJ, Schneider EM, Yeary M, Zimmer M, Jaffe JD, Carr SA, Doench JG, Haining WN, Yates KB, Manguso RT, Bernstein BE. 2020. Epigenetic dysregulation is a defining feature of tumorigenesis and has been implicated in immune escape, yet mechanisms that drive immune evasion are poorly understood. To systematically identify epigenetic factors that modulate the immune sensitivity of tumor cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumor models treated with immune checkpoint blockade. We identified the H3K9-methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as cell-intrinsic mediators of immune escape in tumor cells. We also found that amplification of SETDB1 (1q21) in human tumors is associated with reduced cytotoxic T-cell infiltration and resistance to immune checkpoint blockade. Mechanistically, we demonstrate that SETDB1 represses broad domains, hundreds of kilobases in size, many of which reside within the open genome compartment. These SETDB1 domains are enriched for transposable elements (TEs) and immune gene clusters associated with segmental duplication events, a central mechanism of mammalian genome evolution. SETDB1 loss derepresses latent TE-encoded regulatory elements and proximal immune genes within these repetitive regions, including canonical co-stimulatory ligands, and induces hundreds of putative TE-encoded viral antigens. Our study establishes SETDB1 as an epigenetic checkpoint that suppresses intrinsic immunogenicity in cancer cells, and thus represents a candidate target for immunotherapy.
2020-12-11 | MSV000086580 | MassIVE