Sox2-Evf2 lncRNA mechanisms of chromosome topological control in developing forebrain
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA689838 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13362600_1.fastq.gz | Fastqsanger.gz | |||
| SRR13362600_2.fastq.gz | Fastqsanger.gz | |||
| SRR13362601_1.fastq.gz | Fastqsanger.gz | |||
| SRR13362601_2.fastq.gz | Fastqsanger.gz | |||
| SRR13362602_1.fastq.gz | Fastqsanger.gz |
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Project description:Evf2 lncRNA controls Sox2, BRG1 (Smarca4) and Dlx binding in E13.5 mouse brain ganglionic eminences. Sox2 controls Dlx5/6ultraconserved enhancer (Dlx5/6UCE) interactions across chromosome 6. A subset overlap with Evf2 regulated Dlx5/6UCE interaction sites.
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Project description:The Evf2 long non-coding RNA directs Dlx5/6 ultraconserved enhancer(UCE)-intrachromosomal interactions, regulating genes across a 27 Mb region on chromosome 6 in mouse developing forebrain. Here, we show that Evf2 long-range gene repression occurs through multi-step mechanisms involving the transcription factor Sox2. Evf2 directly interacts with Sox2, antagonizing Sox2 activation of Dlx5/6UCE, and recruits Sox2 to the Dlx5/6eii shadow enhancer and key Dlx5/6UCE interaction sites. Sox2 directly interacts with Dlx1 and Smarca4, as part of the Evf2 ribonucleoprotein complex, forming spherical subnuclear domains (protein pools, PPs). Evf2 targets Sox2 PPs to one long-range repressed target gene (Rbm28), at the expense of another (Akr1b8). Evf2 and Sox2 shift Dlx5/6UCE interactions towards Rbm28, linking Evf2/Sox2 co-regulated topological control and gene repression. We propose a model that distinguishes Evf2 gene repression mechanisms at Rbm28 (Dlx5/6UCE position) and Akr1b8 (limited Sox2 availability). Genome-wide control of RNPs (Sox2, Dlx and Smarca4) shows that co-recruitment influences Sox2 DNA binding. Together, these data suggest that Evf2 organizes a Sox2 PP subnuclear domain and, through Sox2-RNP sequestration and recruitment, regulates chromosome 6 long-range UCE targeting and activity with genome-wide consequences.
| S-EPMC7990859 | biostudies-literature
Project description:We report the distribution of histone H3K4me1 and H3K27ac within the genome of mouse embryonic forebrain. We prepared the chromatin from 11 dpc embryonic forebrain and made chromatin precipitation with antibody against H3K4me1 and H3K27ac (rabbit polyclonal antibody). High-throughput sequencing applied for the ChIP analysis revealed the differential distribution of modified histone within developing forebrain.
2014-11-12 | GSE52280 | GEO
Project description:Sox2 has been studied in several types of human solid tumors. The investigators found that Sox2 had higher expression level in colorectal cancer and metastatic tissues than normal tissues. So the investigators assumed that whether Sox2 plays an important role in the progression and migration of colon cancer.
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Project description:The lack of axonal growth after injury in the adult central nervous system (CNS) is partly due to the presence of growth-inhibitory molecules associated with myelin and the intrinsic growth-state of the injured neurons. To date, three inhibitors have been identified in myelin: Myelin- Associated Glycoprotein (MAG), Nogo A, and Oligodendrocyte-Myelin glycoprotein (OMgp). These three proteins all appear to be located in the periaxonal surface of the myelin membrane placing them in an optimal location to mediate axon-glial interaction. In addition, the three proteins have been shown to bind the same neuronal receptor, known as the Nogo-66 receptor (NgR). It has been hypothesized that inhibition of NgR may be a strategy to increase regeneration, plasticity and functional recovery of the lesioned central nervous system. Strong NgR mRNA expression is observed in the hippocampal pyramidal cell layers (CA1-3) and the granular layer of the dentate gyrus. It has been shown that animals exposed to entorhinal lesions show a biphasic regulation of NgR in the hippocampus, suggesting a tightly regulated mechanism mediated by this receptor. We have access to a transgenic model to over-express NgR in forebrain hippocampal neurons. Preliminary results have shown a phenotypic response in behavior and some molecular markers, as result of NgR overexpression. Knowledge of what genes are reacting in this novel transgenic model may provide insights into what pathways are affected by NgR to control synaptic plasticity in normal animals and during injury. We have access to a bitrasgenic conditional mouse model to everexpress the NgR receptor in forebrain neurons, through the CamKII promoter. This conditional model uses the tetracycline transactivator (tTA), which is expressed through the CamKII promoter. Upon removal of doxycycline, the TetOp target gene becomes active and over-expression of NgR in cells with an active CaMKII promoter is achieved. We will determine gene expression patterns in the dentate gyrus of transgenic animals engineered to over-express NgR through the CamKII promoter (present in several forebrain areas), and upon removal of doxyxycline. We hypothesize that over-expression of NgR in the hippocampus inhibits synaptic plasticity, thereby suppressing the formation of new synapses necessary for the formation of memory. EXPERIMENT 1; - Effects of NgR overexpression in the mature forebrain -; 1) Experimental group: Bitrasgenic + water: Overexpresses NgR in forebrain neurons. In this group, doxyxycline was removed from the drinking water in adult animals. All the control groups were aged matched. 2) Control group: Bitransgenic + doxy: Should control for leakage by the TetOp target gene, or for any effects mediated by doxycycline, as compared to other control groups. 3) Control group: Monotransgenic + water: Should control for any leakage mediated by the TetOp target gene, as compared to other control groups. 4) Control group: Monotrangenic + water: Should control for leakage by the TetOp target gene, or for any effects mediated by doxycycline, as compared to other control groups. EXPERIMENT 2; - Effects of NgR overexpression in the developing forebrain -; We will also analyze the effects of NgR overexpression in bitransgenic animals raised on water. In these animals, the NgR transgene is expressed in the forebrain upon activation of the CamKII promoter. Since neuronal differentiation and neuronal pathways are being formed during development, we anticipate that NgR overexpression (de)effects in these animals will be markedly different to those observed in adult animals. 1) Bitransgenic + water (through entire lifespan): The animals in this group were never treated with doxycycline, and therefore expressed the NgR transgene upon activity of the CamKII promoter. 2) Monotransgenic + water: This control group will control for leakage by the Tet Op gene, or for effects of the tTA expression.
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Project description:Sox2 is expressed by neural stem and progenitor cells, and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors. We used adenoviral E/sox2:EGFP to transduce dissociates of the second trimester human ventricular zone (VZ)/ subventricular zone (SVZ), followed by EGFP-directed fluorescence-activated cell sorting (FACS). The sox2 isolates and unsorted controls from different gestational ages (16-19 wks, n=4) were then subject to RNA extraction and hybridization on Affymetrix microarrays.
2011-02-25 | E-GEOD-27505 | biostudies-arrayexpress
Project description:Sox2 is expressed by neural stem and progenitor cells, and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors.
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