NFI transcription factors regulate zonal olfactory receptor expression
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ABSTRACT:
PROVIDER: PRJNA666396 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR12761400_1.fastq.gz | Fastqsanger.gz | |||
| SRR12761400_2.fastq.gz | Fastqsanger.gz | |||
| SRR12776500_1.fastq.gz | Fastqsanger.gz | |||
| SRR12776500_2.fastq.gz | Fastqsanger.gz |
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Project description:Expression of one out of > 1000 olfactory receptor (OR) genes is stochastic, yet organized into anatomic "zones" along the dorsoventral axis of the olfactory epithelium. Here we profile the gene expression, chromatin state and nuclear architecture of olfactory sensory neurons and olfactory progenitors of different zones. We discovered that zonal OR expression is specified by two processes: low-level polygenic transcription of OR genes in olfactory progenitors, as wells as the chromatin structure and nuclear architecture during olfactory differentiation. Specifically, in cells of any zonal segment, polygenic transcription in olfactory progenitors defines the OR repertoire eligible for OR choice as the cells mature, while an increased level of heterochromatin and chromatin compaction represses ectopic more dorsally expressed ORs. We find that this process is regulated by the NFI family of transcription factors that are expressed in a graded fashion in the olfactory epithelium. Conditional deletion of NFI A, B, and X results in a transformation of the chromatin state and nucellar architecture and an accompanying shift in the preferred OR repertoire.
2023-06-14 | GSE158730 | GEO
Project description:Distant enhancer elements are a major source of specificity in mammalian gene expression. Although enhancers that regulate broad developmental decisions and inducible gene expression have been studied extensively, little is known about regulatory elements that govern monogenic and monoallelic expression. Here, using high throughput epigenetic and genetic techniques we identified a plethora of distant enhancers that regulate monoallelic olfactory receptor (OR) gene expression. Potential OR enhancers have unique, cell type specific epigenetic marks that distinguish them from other neuronal enhancers and correlate with enhancer activity in vivo. Using sequence capture to enrich for these sequences we identified Dnase-protected footprints that reveal novel regulatory sequences and transcription factors required for OR gene activation. Our experiments provide insight to the regulation of OR expression, and describe novel principles and methodologies towards the understanding of transcriptional mechanisms that generate cellular diversity. In vivo examination of H3K79me3 enrichment and DNAse protected footprints on olfactory receptor enhancer sequences. We performed ChIP-seq on native chromatin isolated from the mouse olfactory epithelium using antibodies against H3K79me3. To sequence accessible regions of the genome we treated nuclei with limiting amounts of DNAse I to digest accessible chromatin and perform Dnase Hypersensitivity (DHS)-seq. In the olfactory epithelium, the H enhancer – the first described enhancer for olfactory receptors has a well-defined DNAse I hypersensitivity peak and is flanked by high levels of H3K79me3. We find other intergenic sequences nearby olfactory receptor genes that share the same chromatin signature, and test their function in vivo. TO uncover transcription factor footprints on olfactory receptor enhancers we performed sequence capture of the DHS-seq library to enrich for these sequences. We find multiple DNAse-protected sequences and perform motif analysis on transcription factor footprints to reveal factors involved in olfactory receptor gene regulation.
2014-11-05 | E-GEOD-55174 | biostudies-arrayexpress
Project description:Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development
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Project description:Dendrite and synapse development are critical for establishing appropriate neuronal circuits, and disrupted timing of these events can alter connectivity leading to disordered neural function. In early postnatal development of cerebellar granule neurons (CGNs), the expression of many genes is temporally regulated. Further, NFI (Nuclear Factor I) proteins have been shown to play important roles in the regulation of gene expression in developing CGNs. To identify NFI-regulated genome-wide targets involved in late maturation of mouse CGNs, we performed two groups of microarray expression analysis: (1) temporal expression arrays using 1.5 and 6 day cultures of mouse CGNs representing immature and more mature CGNs, respectively, which identified 844 Temporal-Up or Down genes; and (2) NFI-regulated genes in 6 day CGN cultures that were infected at the time of plating with lentiviral vectors expressing either NFI dominant repressor (NFI-EnR) or EnR control protein. This identified 686 NFI-Up (NFI-EnR down-regulated) or NFI-Down (NFI-EnR up-regulated) genes. Overlap analysis identified 212 temporal genes that were regulated by NFI. These results indicated that NFI plays a pivotal role in the regulation of late CGN maturation.
2012-11-07 | GSE42018 | GEO
Project description:Dendrite and synapse development are critical for establishing appropriate neuronal circuits, and disrupted timing of these events can alter connectivity leading to disordered neural function. In early postnatal development of cerebellar granule neurons (CGNs), the expression of many genes is temporally regulated. Further, NFI (Nuclear Factor I) proteins have been shown to play important roles in the regulation of gene expression in developing CGNs. To identify NFI-regulated genome-wide targets involved in late maturation of mouse CGNs, we performed two groups of microarray expression analysis: (1) temporal expression arrays using 1.5 and 6 day cultures of mouse CGNs representing immature and more mature CGNs, respectively, which identified 844 Temporal-Up or Down genes; and (2) NFI-regulated genes in 6 day CGN cultures that were infected at the time of plating with lentiviral vectors expressing either NFI dominant repressor (NFI-EnR) or EnR control protein. This identified 686 NFI-Up (NFI-EnR down-regulated) or NFI-Down (NFI-EnR up-regulated) genes. Overlap analysis identified 212 temporal genes that were regulated by NFI. These results indicated that NFI plays a pivotal role in the regulation of late CGN maturation. For temporal arrays, mouse CGN progenitors were purified from P6 mouse cerebellum and cultured for either 1.5 or 6 days. Three biological replicates were analyzed for each time point. For NFI arrays, CGN progenitors from P6 mice were transduced upon plating with either NFI-EnR or EnR control lentivirus and cultured 6 days. Four pairs of biological replicates were performed.
2012-11-07 | E-GEOD-42018 | biostudies-arrayexpress
Project description:Purpose: To asses changes in gene expression profiles from the P11 no cre littermate control olfactory bulbs and conditional double knockout olfactory bulbs of Dlx5/6-CIE; Sp8 Flox/Flox; Sp9 Flox/Flox (Sp8/Sp9-DCKO) mice. Methods: Total RNA was isolated and sequenced from the olfactory bulbs of the P11 no cre littermate controls or Sp8/Sp9-DCKO mice in duplicate using an illumina high-seq 2500. Raw data was analyzed using TopHat. Genes were considered changed which performed fold-change>=2 and FDR<=0.05. Changed genes were then filtered to reveal the downstream targets of Sp8 and Sp9. Results: 32 genes were significantly increased and 144 genes were significantly decreased in expression level due to the loss of Sp9 and Sp8 expression.
2016-09-03 | GSE86396 | GEO
Project description:Purpose: To asses changes in gene expression profiles from the P30 wild type littermate control olfactory bulbs and conditional double knockout olfactory bulbs of hGFAP-Cre; Sp8 Flox/Flox; Sp9 Flox/Flox mice. Methods: Total RNA was isolated and sequenced from the olfactory bulbs of the P30 wild type littermate controls or hGFAP-Cre; Sp8 Flox/Flox; Sp9 Flox/Flox mice in tetrad using an illumina high-seq 2500. Raw data was analyzed using TopHat. Genes were considered changed which performed fold-change>=2 and FDR<=0.05. Changed genes were then filtered to reveal the downstream targets of Sp8 and Sp9. Results: 31 genes were significantly increased and 74 genes were significantly decreased in expression level due to the loss of Sp9 and Sp8 expression.
2017-01-04 | GSE93061 | GEO
Project description:We conducted RNA-Seq and in situ hybridization to identify transcriptional profile changes in the Sp8/Sp9-DCKO olfactory bulb. Simultaneously, we did ChIP-Seq with homemade Sp9 antibody to identify Sp9 binding motifs and which changed genes might be the direct targets of transcription factor Sp9. We found that Sp9 directly binded to key genes which are required for olfactory bulb development. Transcription factors Sp8 and Sp9 belong to the same transcription factor family, so we think Sp8 and Sp9 have very similar binding sites of transcriptional regulation.
2016-09-29 | GSE87416 | GEO
Project description:The Nuclear Factor I C (NFI-C) transcription factor has been implicated in TGF-β signaling, extracellular matrix deposition and skin appendage pathologies. We performed a global gene expression analysis in NFI-C-/- and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-β1. Misregulated genes featured a prominent over-representation of regulators of connective tissue inflammation and repair.
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Project description:The mechanisms by which the fetal type b-globin-like genes HBG1 and HBG2 are silenced in adult erythroid precursor cells is a basic biology question in human development. Reversal of such mechanisms is beneficial for b hemoglobinopathies, such as sickle cell disease (SCD). A CRISPR-Cas9 genetic screen uncovered two members of the NFI transcription factor family – NFIA and NFIX – as novel HBG1/2 repressors. Both factors are expressed at elevated levels in adult erythroid cells, and their single or combined depletion revealed cooperativity in HBG1/2 regulation in cultured cells and human-to-mouse xenotransplant experiments, as well as in preventing sickling of SCD-derived erythroblasts. Genomic profiling, gene editing and in vitro binding assays demonstrated that the potent concerted activity of NFIA and NFIX factors is explained in part by their ability to activate expression of BCL11A, a known silencer of the HBG1/2 genes, and in part by repressing the HBG1/2 genes via two direct binding sites. NFI factors emerge as versatile regulators of the fetal-to-adult switch in b-globin production.
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