Project description:SOX2 is part of the core network of transcription factors regulating embryonic stem cell pluripotency. We found that SOX2 has the ability to remain bound to mitotic chromosomes, in contrast to most transcription factors that are excluded from mitotic chromatin as transcription shuts down. We obtained a highly purified population of mitotic mouse embryonic stem cells and compared the genome-wide binding profile of SOX2 to that in asynchronous cells by Chromatin Immunoprecipitation followed by high throughput sequencing (ChIP-seq), and show that SOX2 remains bound to a small set of genes during mitosis.
Project description:Chickarmane2006 - Stem cell switch reversible
Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch.
This model is described in the article:
Transcriptional dynamics of the embryonic stem cell switch.
Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C
PLoS Computational Biology. 2006; 2(9):e123
Abstract:
Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains on even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
This model is hosted on BioModels Database
and identified by: MODEL7957907314
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
Project description:Chickarmane2006 - Stem cell switch irreversible
Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch.
This model is described in the article:
Transcriptional dynamics of the embryonic stem cell switch.
Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C
PLoS Computational Biology. 2006; 2(9):e123
Abstract:
Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains on even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
This model is hosted on BioModels Database
and identified by: MODEL7957942740
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
Project description:dataset contains 8 samples: 2 asynchronous and 2 mitotically synchronized populations (one with 90% and another with 95% mitotic purity) and 4 corresponding inputs. Cells were synchonized for 10h with colchicine at 330nM. asyncronous samples (interphase) were sonicated and prepared in parallel with same cell number as the corresponding mitotic samples. Fetal neural stem/progenitor cells were obtained from mouse telencephalon (ventral region) at E13.5. This data generated 4 genome-wide binding profiles corresponding to Brn2 (POU3f2) binding sites, aligned to MM9 mus musculus dataset.
Project description:We executed CUT&RUN-seq for SWI/SNF components ARID1A, BRD9, SMARCA4, SMARCB1, SMARCE1, as well as ESRRB, SOX2, and EZH2 in asynchronous and mitotic cells and reported that, in asynchronous cells, ARID1A localized primarily at enhancer regions and EZH2 preferentially deposited at bivalent promoters and silent enhancer domains. The remaining factors were enriched at both TSS/promoters and to varying degrees at active enhancers. Unexpectedly, in mitosis, the chromatin regulatory factors almost all tethered at proximal gene regions with very little binding at enhancers. While the SWI/SNF subunits were bound principally at promoters, EZH2, the catalytic subunit of Polycomb Repressive Complex 2 was bound at both promoters and silent enhancers in mitotic cells. Moreover, we reported that upon the degradation of SMARCE1 in mitosis, the occupancy of SOX2, ESRRB, and EZH2 on mitotic chromatin was disrupted.
Project description:Here we have developed a method to identify chromatin-bound partners of a protein of interest by selective isolation of chromatin-associated proteins (SICAP) followed by mass spectrometry. We applied SICAP to identify chromatin-binding proteins associated to Oct4, Sox2 and Nanog in mouse embryonic stem (ES) cells.
Project description:We performed ChIP-seq for H3K4me3, H3K27ac, H3K4me1, H3K27me3, H3K36me3, H3K9me3, and H4K20me3 to characterize chromatin states and investigated SOX2 deposition in asynchronous and mitotic cells.