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Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus non-ciliated cells [RNA-seq]

ABSTRACT: Members of the NSL histone acetyltransferase complex are involved in multi-organ developmental syndromes. While the NSL complex is known for its importance in early development, its role in fully differentiated cells remains enigmatic. Using a kidney-specific model, we discovered that deletion of NSL complex members KANSL2 or KANSL3 in post-mitotic podocytes led to catastrophic kidney dysfunction. A systematic comparison of two primary differentiated cell types revealed that the NSL complex is a master regulator of intraciliary transport genes in both dividing and non-dividing cells. NSL complex ablation led to loss of cilia and impaired sonic hedgehog pathway in ciliated fibroblasts. By contrast, non-ciliated podocytes responded with altered microtubule dynamics and obliterated podocyte functions. Finally, overexpression of wild type but not a double zinc-finger (ZF-ZF)-domain mutant of KANSL2 rescued the transcriptional defects, revealing a critical function of this domain in NSL complex assembly and function. Thus, the NSL complex targets exhibit bifurcation of functions to enable diversity of specialized outcomes in differentiated cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE225433 | GEO | 2023/07/31

REPOSITORIES: GEO

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Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus non-ciliated cells [ChIP-seq]

Project description:Members of the NSL histone acetyltransferase complex are involved in multi-organ developmental syndromes. While the NSL complex is known for its importance in early development, its role in fully differentiated cells remains enigmatic. Using a kidney-specific model, we discovered that deletion of NSL complex members KANSL2 or KANSL3 in post-mitotic podocytes led to catastrophic kidney dysfunction. A systematic comparison of two primary differentiated cell types revealed that the NSL complex is a master regulator of intraciliary transport genes in both dividing and non-dividing cells. NSL complex ablation led to loss of cilia and impaired sonic hedgehog pathway in ciliated fibroblasts. By contrast, non-ciliated podocytes responded with altered microtubule dynamics and obliterated podocyte functions. Finally, overexpression of wild type but not a double zinc-finger (ZF-ZF)-domain mutant of KANSL2 rescued the transcriptional defects, revealing a critical function of this domain in NSL complex assembly and function. Thus, the NSL complex targets exhibit bifurcation of functions to enable diversity of specialized outcomes in differentiated cells.

2023-07-31 | GSE225432 | GEO

Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus non-ciliated cells [ChIP-Seq 2]

2023-07-31 | GSE235243 | GEO

ChIP-seq of MOF, MSL and NSL complex members in mouse ES cells and neuronal progenitors

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.

2014-06-03 | E-GEOD-51746 | biostudies-arrayexpress

RNA-seq of mouse ES cells depleted of MOF, MSL1, MSL2 or KANSL3

Project description:We have studied the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by binding to promoters as well as TSS-distal enhancer regions. In contrast to flies, the MSL complex is not enriched on the X chromosome yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix ncRNA, the major repressor of Xist lncRNA. MSL depletion leads to severely decreased Tsix expression, reduced REX1 recruitment, and consequently accumulation of Xist RNA in ESCs. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs. We have performed ChIP-seq of KANSL3, MCRS1, MOF, MSL1 and MSL2 in mouse ESCs, and KANSL3, MOF and MSL2 in NPCs, in duplicate and normalised against their inputs. We have also performed RNA-seq following knockdown of Kansl3, Mof, Msl1 and Msl2 mouse embryonic stem cells in triplicate. NB: Kansl3 and Mof knockdown-RNAseq are analyzed against their own scrambled controls, and Msl1 and Msl2 against another scrambled control triplicate.

2014-06-03 | E-GEOD-57698 | biostudies-arrayexpress

ChIP-seq of MOF, MSL and NSL complex members in mouse ES cells and neuronal progenitors

2014-06-03 | GSE51746 | GEO

The Ciliated Cell Transcriptome: Ciliated Mouse Tracheal Epithelial Cells vs Control Non-ciliated Mouse Tracheal Epithelial Cells during in Vitro Differentiation

Project description:Transcriptional profiling of ciliating mouse tracheal epithelial cells compared to non-ciliating cells at two timepoints, ALI+4 and ALI+12, during differentiation in vitro. These cells are obtained from a transgenic mouse expressing GFP from a human FOXJ1 promoter, so that cells destined to become ciliated can be sorted by FACS based on their expression of GFP. Likewise, the control non-ciliated cells are identified by their lack of GFP expression. Ciliated cells were compared to Universal Reference RNA, and non-ciliated cells were compared to Universal Reference RNA. Two-color arrays were used to compare non-ciliated cells, or ciliated cell samples taken at 4 days or 12 days after establishment of the air-liquid interface (ALI), to a Universal Reference RNA. Ciliated cells vs. Universal Reference RNA or Non-ciliated cells vs. Universal Reference RNA. 3 biological replicates from independently grown and harvested cell cultures were performed for non-ciliated cells, 5 biological replicates were performed for a ciliated cell samples at ALI+12, and 3 biological replicates plus 2 technical replicates were performed for ciliated cell samples at ALI+4.

2012-11-29 | E-GEOD-42500 | biostudies-arrayexpress

Generation of functional ciliated cholangiocytes from human pluripotent stem

Project description:We report on the successful generation of functional ciliated cholangoocytes from hPSCs that will provide new opportunities to study and treat diseases of the liver. Both monolayer- and organoid-derived cells are adaptable for further bioengineering approcahes to produce more complex hPSC-deived liver tissue with biliary ductal structures. Additionally, the successful engraftment of differentiated cholangiocytes in the liver of immune-imcompetent mice provides the basis for developing novel therapeutic strategies to treat cholangiopathies.

2021-10-03 | GSE175502 | GEO

The Ciliated Cell Transcriptome: Ciliated Mouse Tracheal Epithelial Cells vs Control Non-ciliated Mouse Tracheal Epithelial Cells during in Vitro Differentiation

2012-11-29 | GSE42500 | GEO

microRNAs signatures of Xenopus laevis embryo epidermis at stage 11 (non ciliated) and 26 (ciliated) using high throughput sequencing

Project description:Epidermis of Xenopus embryos forms a mucociliary epithelium constituted of basal, scattered, secreting and ciliated cells and is histologically similar to human airway mucociliary epithelium. We compared microRNAs signatures of epidermis of Xenopus embryos at stage 11.5 (gastrula, non ciliated epidermis) and at stage 26 (tailbud, ciliated epidermis). 2 technical replicates of a pool of 50 explants for each stage 11.5 (non ciliated) and 26 (ciliated) of Xenopus laevis development

2011-06-06 | E-GEOD-22146 | biostudies-arrayexpress

microRNAs signatures of Xenopus laevis embryo epidermis at stage 11 (non ciliated) and 26 (ciliated) using high throughput sequencing

2011-06-07 | GSE22146 | GEO

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