scholarly journals Core transcription factors, Oct4, Sox2 and Nanog, individually form complexes with nucleophosmin (Npm1) to control embryonic stem (ES) cell fate determination

Aging ◽  
2010 ◽  
Vol 2 (11) ◽  
pp. 815-822 ◽  
Author(s):  
Helena Johansson ◽  
Stina Simonsson
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Cell Fate Determination ◽  
Es Cell ◽  
Fate Determination

scholarly journals POGZ controls embryonic stem cell self-renewal and pluripotency by association with esBAF and HP1

2021 ◽  
Author(s):  
Xiaoyun Sun ◽  
Linxi Cheng ◽  
Yuhua Sun
Keyword(s):  
Cell Fate ◽  
Neurodevelopmental Disorders ◽  
Embryonic Stem ◽  
Autism Spectrum ◽  
Specific Gene ◽  
Open Chromatin ◽  
Cell Fate Determination ◽  
Chromatin Remodeler ◽  
Self Renewal ◽  
Fate Determination

AbstractPOGZ, which encodes a multi-domain transcription factor, has been found frequently mutated in neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its function in ESC self-renewal and pluripotency, cell fate determination as well as in transcriptional regulation. Here, using embryonic stem cells (ESCs) as model, we show that POGZ plays key roles in the maintenance of ESC and cell fate determination by association with the SWI-SNW chromatin remodeler complex and heterochromatin protein 1 (HP1) proteins. POGZ is essential for the maintenance of ESC undifferentiated state, and loss of POGZ leads to ESC differentiation, likely by up-regulation of primitive endoderm and mesoderm lineage genes and by down-regulation of pluripotency-related genes. Mechanistically, POGZ may control ESC-specific gene expression by association with chromatin remodeler complex esBAF and HP1s, and they can form a PBH triplex. POGZ functions primarily to maintain an open chromatin, as loss of POGZ leads to a reduced chromatin accessibility. Regulation of chromatin under control of POGZ depends on esBAF complex. POGZ is extensively co-localized with OCT4/NANOG genome wide. Taken together, we propose that POGZ is a pluripotency-associated factor, and its absence in ESCs causes failure to maintain a proper ESC-specific chromatin state and transcriptional circuitry of pluripotency, which eventually leads to ESC self-renewal and pluripotency defects. Our work provides important insights into the role of POGZ in ESC self-renewal and pluripotency as well as regulation of transcription, which will be useful for understanding the etiology of neurodevelopmental disorders by POGZ mutation.

scholarly journals LncRNA Platr22 promotes super-enhancer activity and stem cell pluripotency

2020 ◽  
Author(s):  
Pixi Yan ◽  
J Yuyang Lu ◽  
Jing Niu ◽  
Juntao Gao ◽  
Michael Q Zhang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Noncoding Rna ◽  
Embryonic Stem ◽  
Cell Fate Determination ◽  
Enhancer Activity ◽  
Lncrna Gene ◽  
Fate Determination ◽  
Super Enhancer ◽  
Stem Cell Pluripotency ◽  
Active Transcription

Abstract Super-enhancers (SEs) comprise large clusters of enhancers, which are co-occupied by multiple lineage-specific and master transcription factors, and play pivotal roles in regulating gene expression and cell fate determination. However, it is still largely unknown whether and how SEs are regulated by the non-coding portion of the genome. Here, through genome-wide analysis, we found that long noncoding RNA (lncRNA) genes preferentially lie next to SEs. In mouse embryonic stem cells (mESCs), depletion of SE-associated lncRNA transcripts dysregulated the activity of their nearby SEs. Specifically, we revealed a critical regulatory role of the lncRNA gene Platr22 in modulating the activity of a nearby SE and the expression of the nearby pluripotency regulator ZFP281. Through these regulatory events, Platr22 contributes to pluripotency maintenance and proper differentiation of mESCs. Mechanistically, Platr22 transcripts coat chromatin near the SE region and interact with DDX5 and hnRNP-L. DDX5 further recruits p300 and other factors related to active transcription. We propose that these factors assemble into a transcription hub, thus promoting an open and active epigenetic chromatin state. Our study highlights an unanticipated role for a class of lncRNAs in epigenetically controlling the activity and vulnerability to perturbation of nearby SEs for cell fate determination.

scholarly journals FGF-induced Pea3 transcription factors program the genetic landscape for cell fate determination

PLoS Genetics ◽  
2018 ◽  
Vol 14 (9) ◽  
pp. e1007660 ◽  
Author(s):  
Ankur Garg ◽  
Abdul Hannan ◽  
Qian Wang ◽  
Tamica Collins ◽  
Siying Teng ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Genetic Landscape

scholarly journals Chromatin Assembly Factor 1 (CAF-1) facilitates the establishment of facultative heterochromatin during pluripotency exit

2019 ◽  
Vol 47 (21) ◽  
pp. 11114-11131 ◽  
Author(s):  
Liang Cheng ◽  
Xu Zhang ◽  
Yan Wang ◽  
Haiyun Gan ◽  
Xiaowei Xu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Embryonic Stem ◽  
Chromatin Assembly ◽  
Nuclear Antigen ◽  
Gene Promoters ◽  
Cell Fate Determination ◽  
Nucleosome Assembly ◽  
Fate Determination ◽  
Chromatin Assembly Factor ◽  
Assembly Factor

Abstract Establishment and subsequent maintenance of distinct chromatin domains during embryonic stem cell (ESC) differentiation are crucial for lineage specification and cell fate determination. Here we show that the histone chaperone Chromatin Assembly Factor 1 (CAF-1), which is recruited to DNA replication forks through its interaction with proliferating cell nuclear antigen (PCNA) for nucleosome assembly, participates in the establishment of H3K27me3-mediated silencing during differentiation. Deletion of CAF-1 p150 subunit impairs the silencing of many genes including Oct4, Sox2 and Nanog as well as the establishment of H3K27me3 at these gene promoters during ESC differentiation. Mutations of PCNA residues involved in recruiting CAF-1 to the chromatin also result in defects in differentiation in vitro and impair early embryonic development as p150 deletion. Together, these results reveal that the CAF-1-PCNA nucleosome assembly pathway plays an important role in the establishment of H3K27me3-mediated silencing during cell fate determination.

scholarly journals Endogenous fluctuations of OCT4 and SOX2 bias pluripotent cell fate decisions

2018 ◽  
Author(s):  
Daniel Strebinger ◽  
Cédric Deluz ◽  
Elias T. Friman ◽  
Subashika Govindan ◽  
Andrea B. Alber ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Es Cells ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Directed Differentiation ◽  
Es Cell ◽  
Endogenous Fluctuations ◽  
Cell Fate Decisions ◽  
Oct4 Protein

AbstractSOX2 and OCT4 are pioneer transcription factors playing a key role in embryonic stem (ES) cell self-renewal and differentiation. However, how temporal fluctuations in their expression levels bias lineage commitment is unknown. Here we generated knock-in reporter fusion ES cell lines allowing to monitor endogenous SOX2 and OCT4 protein fluctuations in living cells and to determine their impact on mesendodermal and neuroectodermal commitment. We found that small differences in SOX2 and OCT4 levels impact cell fate commitment in G1 but not in S phase. Elevated SOX2 levels modestly increased neuroectodermal commitment and decreased mesendodermal commitment upon directed differentiation. In contrast, elevated OCT4 levels strongly biased ES cell towards both neuroectodermal and mesendodermal fates. Using ATAC-seq on ES cells gated for different endogenous SOX2 and OCT4 levels, we found that high OCT4 levels increased chromatin accessibility at differentiation-associated enhancers. This suggests that small endogenous fluctuations of pioneer transcription factors can bias cell fate decisions by concentration-dependent priming of differentiation-associated enhancers.

scholarly journals Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses

2000 ◽  
Vol 14 (24) ◽  
pp. 3191-3203
Author(s):  
David M. Adelman ◽  
Marina Gertsenstein ◽  
Andras Nagy ◽  
M. Celeste Simon ◽  
Emin Maltepe
Keyword(s):  
Cell Fate ◽  
Es Cells ◽  
Hypoxia Inducible Factor ◽  
Embryonic Stem ◽  
Giant Cells ◽  
Cell Fate Determination ◽  
Placental Development ◽  
Fate Determination

Placental development is profoundly influenced by oxygen (O2) tension. Human cytotrophoblasts proliferate in vitro under low O2 conditions but differentiate at higher O2 levels, mimicking the developmental transition they undergo as they invade the placental bed to establish the maternal–fetal circulation in vivo. Hypoxia-inducible factor-1 (HIF-1), consisting of HIF-1α and ARNT subunits, activates many genes involved in the cellular and organismal response to O2deprivation. Analysis of Arnt−/− placentas reveals an aberrant cellular architecture due to altered cell fate determination of Arnt−/− trophoblasts. Specifically, Arnt−/− placentas show greatly reduced labyrinthine and spongiotrophoblast layers, and increased numbers of giant cells. We further show that hypoxia promotes the in vitro differentiation of trophoblast stem cells into spongiotrophoblasts as opposed to giant cells. Our results clearly establish that O2 levels regulate cell fate determination in vivo and that HIF is essential for mammalian placentation. The unique placental phenotype of Arnt−/− animals also provides an important tool for studying the disease of preeclampsia. Interestingly, aggregation of Arnt−/− embryonic stem (ES) cells with tetraploid wild-type embryos rescues their placental defects; however, these embryos still die from yolk sac vascular and cardiac defects.

scholarly journals ANANSE: An enhancer network-based computational approach for predicting key transcription factors in cell fate determination

2020 ◽  
Author(s):  
Quan Xu ◽  
Georgios Georgiou ◽  
Gert Jan C. Veenstra ◽  
Huiqing Zhou ◽  
Simon J. van Heeringen
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
Cell Fate Determination ◽  
Cell Type ◽  
Fate Determination ◽  
Cell Type Specific ◽  
Gene Regulatory

AbstractProper cell fate determination is largely orchestrated by complex gene regulatory networks centered around transcription factors. However, experimental elucidation of key transcription factors that drive cellular identity is currently often intractable. Here, we present ANANSE (ANalysis Algorithm for Networks Specified by Enhancers), a network-based method that exploits enhancer-encoded regulatory information to identify the key transcription factors in cell fate determination. As cell type-specific transcription factors predominantly bind to enhancers, we use regulatory networks based on enhancer properties to prioritize transcription factors. First, we predict genome-wide binding profiles of transcription factors in various cell types using enhancer activity and transcription factor binding motifs. Subsequently, applying these inferred binding profiles, we construct cell type-specific gene regulatory networks, and then predict key transcription factors controlling cell fate conversions using differential gene networks between cell types. This method outperforms existing approaches in correctly predicting major transcription factors previously identified to be sufficient for trans-differentiation. Finally, we apply ANANSE to define an atlas of key transcription factors in 18 normal human tissues. In conclusion, we present a ready-to-implement computational tool for efficient prediction of transcription factors in cell fate determination and to study transcription factor-mediated regulatory mechanisms. ANANSE is freely available at https://github.com/vanheeringen-lab/ANANSE.

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