Project description:This SuperSeries is composed of the following subset Series: GSE30989: MOF-containing NSL complex specifically binds promoters of most, but stimulates only a specific subset of, housekeeping genes (ChIP-chip dataset) GSE30990: MOF-containing NSL complex specifically binds promoters of most, but stimulates only a specific subset of, housekeeping genes (expression dataset) Refer to individual Series
Project description:The MOF-containing NSL complex binds to many but not all promoters of active genes and potentially contributes to their proper gene expression. It is currently unknown what determines whether an active gene is bound or not. Here, we provide evidence that the NSL complex primarily targets active promoters of most housekeeping genes. There, it co-localizes with the chromatin remodeler NURF and the histone methyltransferase Trithorax. Moreover, despite binding to most housekeeping genes, the NSL complex regulates only a subset of them, which are depleted for certain insulator binding-proteins and enriched for the core promoter motif “Ohler 5”. We suggest that the combination of general chromatin factors and core promoter motifs is predictive for whether a housekeeping gene is transcriptionally regulated by the NSL complex. Transcriptome expression profiling comparing NSL1 RNAi-depleted cells with control RNAi cells using Affymetrix microarrays.
Project description:The MOF-containing NSL complex binds to many but not all promoters of active genes and potentially contributes to their proper gene expression. It is currently unknown what determines whether an active gene is bound or not. Here, we provide evidence that the NSL complex primarily targets active promoters of most housekeeping genes. There, it co-localizes with the chromatin remodeler NURF and the histone methyltransferase Trithorax. Moreover, despite binding to most housekeeping genes, the NSL complex regulates only a subset of them, which are depleted for certain insulator binding-proteins and enriched for the core promoter motif “Ohler 5”. We suggest that the combination of general chromatin factors and core promoter motifs is predictive for whether a housekeeping gene is transcriptionally regulated by the NSL complex.
Project description:The MOF-containing NSL complex binds to many but not all promoters of active genes and potentially contributes to their proper gene expression. It is currently unknown what determines whether an active gene is bound or not. Here, we provide evidence that the NSL complex primarily targets active promoters of most housekeeping genes. There, it co-localizes with the chromatin remodeler NURF and the histone methyltransferase Trithorax. Moreover, despite binding to most housekeeping genes, the NSL complex regulates only a subset of them, which are depleted for certain insulator binding-proteins and enriched for the core promoter motif “Ohler 5”. We suggest that the combination of general chromatin factors and core promoter motifs is predictive for whether a housekeeping gene is transcriptionally regulated by the NSL complex.
Project description:The MOF-containing NSL complex binds to many but not all promoters of active genes and potentially contributes to their proper gene expression. It is currently unknown what determines whether an active gene is bound or not. Here, we provide evidence that the NSL complex primarily targets active promoters of most housekeeping genes. There, it co-localizes with the chromatin remodeler NURF and the histone methyltransferase Trithorax. Moreover, despite binding to most housekeeping genes, the NSL complex regulates only a subset of them, which are depleted for certain insulator binding-proteins and enriched for the core promoter motif “Ohler 5”. We suggest that the combination of general chromatin factors and core promoter motifs is predictive for whether a housekeeping gene is transcriptionally regulated by the NSL complex. ChIP-chip profiling of NSL1 in adult male and female whole fly extracts and the embryonically derived male S2 cell line.
Project description:We assessed the genome-wide binding of the histone acetylase MOF and members of its two associated complexes, the male-specific lethal and the non-specific lethal complex (MSL, NSL). We generated ChIP-seq profiles for MOF, MSL1, MSL2, KANSL3, and MCRS1 from mouse embryonic stem cells and neuronal progenitor cells. By using two replicates per sample and stringent filtering criteria, we identify five basic groups of genome regions where the proteins show either mutual or exclusive binding. We find that the NSL complex members (KANSL3, MCRS1) target the TSSs of broadly expressed genes with housekeeping functions in both cell types. MOF and particularly the MSL complex target a subset of these NSL-complex-targets, too. In addition, we find several thousand TSS-distal binding sites, particularly in ESCs, where KANSL3, MSL2 and MCRS1 show strong enrichments for annotated ESC enhancers. The vast majority of the binding to these ESC distal regulatory elements is lost in NPCs. Finally, we identify mostly intronic and intergenic regions with predominant MSL2 enrichments without the presence of its known interactors. These binding sites do not overlap with ESC marks of active chromatin (e.g. DNase hypersensitivity sites), but the they increase in number upon differentiation and we detect a strong signature of the (CAGA)n motif. Our study provides the first comprehensive analysis of MOF in the context of its two complexes in the mouse and reveals shared as well as distinct and dynamic functions for gene regulation and pluripotency. ChIP-seq of MOF and members of its associated complexes (MSL complex: MSL1, MSL2; NSL complex: KANSL3, MCRS1) in male mouse embryonic stem cells and neuronal progenitor cells derived from them.
Project description:We assessed the genome-wide binding of the histone acetylase MOF and members of its two associated complexes, the male-specific lethal and the non-specific lethal complex (MSL, NSL). We generated ChIP-seq profiles for MOF, MSL1, MSL2, KANSL3, and MCRS1 from mouse embryonic stem cells and neuronal progenitor cells. By using two replicates per sample and stringent filtering criteria, we identify five basic groups of genome regions where the proteins show either mutual or exclusive binding. We find that the NSL complex members (KANSL3, MCRS1) target the TSSs of broadly expressed genes with housekeeping functions in both cell types. MOF and particularly the MSL complex target a subset of these NSL-complex-targets, too. In addition, we find several thousand TSS-distal binding sites, particularly in ESCs, where KANSL3, MSL2 and MCRS1 show strong enrichments for annotated ESC enhancers. The vast majority of the binding to these ESC distal regulatory elements is lost in NPCs. Finally, we identify mostly intronic and intergenic regions with predominant MSL2 enrichments without the presence of its known interactors. These binding sites do not overlap with ESC marks of active chromatin (e.g. DNase hypersensitivity sites), but the they increase in number upon differentiation and we detect a strong signature of the (CAGA)n motif. Our study provides the first comprehensive analysis of MOF in the context of its two complexes in the mouse and reveals shared as well as distinct and dynamic functions for gene regulation and pluripotency.
Project description:Histone acetylation is associated with open chromatin and transcriptionally active genes. Specifically, acetylation of lysine 16 on histone H4 (H4K16ac) has been shown to prevent the assembly of nucleosomal arrays in vitro. This modification is catalyzed by the MYST-family histone acetyltransferase KAT8 (also known as MOF and MYST1), which is part of two distinct chromatin-associated complexes: NSL and MSL. While extensively studied in Drosophila, the functions of H4K16ac and the two KAT8-containing complexes in mammalian cells are not well understood. Here, we demonstrate a surprising complex-dependent activity of KAT8. We found that KAT8 catalyzes H4K5 and H4K8 acetylation as part of the NSL complex, whereas it catalyzes the bulk of H4K16 acetylation as part of the MSL complex. Furthermore, we show that the core proteins of the MSL complex and H4K16ac are not required for cell proliferation and global chromatin accessibility, whereas the NSL complex is essential for cell survival, as it is enriched at the promoters of housekeeping genes and is required for their transcription initiation. In summary, we show that KAT8 switches catalytic activity and function depending on its associated proteins, and that, as part of the NSL complex, it catalyzes H4K5 and H4K8 acetylation required for the expression of genes essential for cell survival