Epigenetic misactivation of a distal developmental enhancer drives SOX2 overexpression in multiple cancer subtypes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE132344 | GEO | 2023/03/16
REPOSITORIES: GEO
Similar Datasets
Project description:We report the effect on genome-wide gene expression after deletion of an enhancer region downstream of Sox2 in F1 ES cells. The Sox2 transcription factor must be robustly transcribed in embryonic stem (ES) cells to maintain pluripotency. Reporter assays reveal novel enhancers, including two enhancers over 100 kb downstream (SRR107 and SRR111) which, through the formation of chromatin loops, localise to the Sox2 promoter in ES cells. Using CRISPR/Cas9 we deleted a region containing these two enhancers, which we term the Sox2 control region (SCR). This deletion revealed that the SCR is required for Sox2 transcription in ES cells. Furthermore, homozygous deletion of this distal Sox2 control region (SCR) caused significant reduction in Sox2 mRNA and protein levels, loss of ES cell colony morphology, genome-wide changes in gene expression and impaired neuroectodermal formation upon spontaneous differentiation to embryoid bodies. Together these data identify a distal control region essential for Sox2 transcription in ES cells. Examination of PolA+ RNA after heterozygous and homozygous enhancer deletion in F1 ES cells (M. musculus129 x M. castaneus).
2014-11-19 | E-GEOD-58339 | biostudies-arrayexpress
Project description:We report the effect on genome-wide gene expression after deletion of an enhancer region downstream of Sox2 in F1 ES cells. The Sox2 transcription factor must be robustly transcribed in embryonic stem (ES) cells to maintain pluripotency. Reporter assays reveal novel enhancers, including two enhancers over 100 kb downstream (SRR107 and SRR111) which, through the formation of chromatin loops, localise to the Sox2 promoter in ES cells. Using CRISPR/Cas9 we deleted a region containing these two enhancers, which we term the Sox2 control region (SCR). This deletion revealed that the SCR is required for Sox2 transcription in ES cells. Furthermore, homozygous deletion of this distal Sox2 control region (SCR) caused significant reduction in Sox2 mRNA and protein levels, loss of ES cell colony morphology, genome-wide changes in gene expression and impaired neuroectodermal formation upon spontaneous differentiation to embryoid bodies. Together these data identify a distal control region essential for Sox2 transcription in ES cells.
2014-11-19 | GSE58339 | GEO
Project description:The pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although a lot of previous studies have identified key factors regulating this core network in trans, the contribution of cis-regulatory DNA sequences on the transcription of these key pluripotency factors remains elusive. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around Sox2 gene and predicted only one 13kb-long enhancer located 100kb downstream of Sox2 in mouse ES cells. This enhancer is occupied by Oct4, Sox2, Nanog, and mediator complex and forms a long-range DNA looping to Sox2 locus. We hypothesized that this enhancer is critical for Sox2 gene expression and tested this hypothesis by deleting this entire 13-kb enhancer with a simple highly-efficient double-excision CRISPR strategy. Allele-specific of Sox2 transcripts in heterozygous enhancer-deletion clones showed that the enhancer affects expression through a cis-acting mechanism. Strikingly, although this distal enhancer is not conserved in other mammals including human, it is responsible for over 90% of Sox2 expression in mouse ESCs. Taken together, our results provide direct evidence that in mouse ESCs, Sox2 transcription is primarily driven by a species-specific distal enhancer, which may provide new perspectives explaining the physiological difference between human and mouse ES cells. This dataset include ChIP-seq of H3K4me3 and H3K27ac in a hybrid mouse ES cells (F123). H3K27ac in J1 mouse ES cells. And RNA-seq in F123 mESCs with complete Sox2 enhancer deletion or enhancer haploinsufficient clones.
2014-12-09 | E-GEOD-60763 | biostudies-arrayexpress
Project description:The pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although a lot of previous studies have identified key factors regulating this core network in trans, the contribution of cis-regulatory DNA sequences on the transcription of these key pluripotency factors remains elusive. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around Sox2 gene and predicted only one 13kb-long enhancer located 100kb downstream of Sox2 in mouse ES cells. This enhancer is occupied by Oct4, Sox2, Nanog, and mediator complex and forms a long-range DNA looping to Sox2 locus. We hypothesized that this enhancer is critical for Sox2 gene expression and tested this hypothesis by deleting this entire 13-kb enhancer with a simple highly-efficient double-excision CRISPR strategy. Allele-specific of Sox2 transcripts in heterozygous enhancer-deletion clones showed that the enhancer affects expression through a cis-acting mechanism. Strikingly, although this distal enhancer is not conserved in other mammals including human, it is responsible for over 90% of Sox2 expression in mouse ESCs. Taken together, our results provide direct evidence that in mouse ESCs, Sox2 transcription is primarily driven by a species-specific distal enhancer, which may provide new perspectives explaining the physiological difference between human and mouse ES cells.
2014-12-09 | GSE60763 | 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.
| 2124687 | ecrin-mdr-crc
Project description:Specification of Sox2+ proneurosensory progenitors within otic ectoderm is a prerequisite for the production of sensory cells and neurons for hearing. However, the underlying molecular mechanisms driving this lineage specification remain unknown. Here, we show that Brg1-based SWI/SNF chromatin-remodeling complex interacts with the neurosensory-specific transcriptional regulators Eya1/Six1 to induce Sox2 expression and proneurosensory-lineage specification. Ablation of the ATPase-subunit Brg1 or both Eya1/Six1 results in loss of Sox2 expression and lack of neurosensory identity. Brg1 and Six1 co-occupy three distal 3' Sox2 enhancers and Brg1-recruitment to these regions is disrupted in Eya1- or Six1-null otocyst. Eya1 as a coactivator of Six1 synergistically regulates the activity of these enhancers, which drives expression in otic neurosensory cells in response to binding to Six1. Thus, through interaction with Six1/Eya1, the Brg1-based SWI/SNF complex specifies otic proneurosensory lineage. Furthermore, genome-wide and transcriptome analyses reveal that Brg1 also suppresses expression of non-otic genes.
2021-06-04 | GSE158167 | GEO
Project description:We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells, that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells). Human lung squamous BEAS-2B cells were transduced for Control or SOX2 expression, and their transcriptomes compared using Affymetrix arrays.
2010-02-21 | E-GEOD-14883 | biostudies-arrayexpress
Project description:In this dataset, we include the expression data obtained from rat Schwann cells overepressing GFP (control) or Sox2/GFP to identfiy Sox2 tragets in Schwann cells. An in vitro microarray analysis of GFP (control) and Sox2/GFP overexpressing Schwann cells
2018-12-18 | GSE123915 | GEO
Project description:We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells, that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells).
2010-02-10 | GSE14883 | GEO
