scholarly journals Cell signaling coordinates global Polycomb Repressive Complex 2 recruitment and gene expression in murine embryonic stem cells

2019 ◽  
Author(s):  
Mohammad B. Aljazi ◽  
Yuen Gao ◽  
Yan Wu ◽  
George I. Mias ◽  
Jin He
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Cell Signaling ◽  
Embryonic Stem ◽  
Erk Signaling ◽  
Gene Promoters ◽  
Polycomb Repressive Complex 2 ◽  
Murine Embryonic Stem Cells

SummaryThe recruitment of Polycomb repressive complex 2 (PRC2) to gene promoters is critical for its function in repressing gene expression in murine embryonic stem cells (mESCs). However, previous studies have demonstrated although the expression of early lineage-specific genes is largely repressed, the genome-wide PRC2 occupancy is unexpectedly reduced in naïve mESCs. In this study, we provide evidence to show the FGF/ERK signaling determines the global PRC2 occupancy through regulating the expression of PRC2-recruting factor JARID2 in naïve mESCs. At the transcriptional level, the de-repression of bivalent genes is predominantly determined by the presence of cell signaling-associated transcription factors but not the status of PRC2 occupancy at gene promoters. Hence, this study not only reveals a key molecular mechanism by which the FGF/ERK signaling in regulating the PRC2 occupancy in mESCs, but also elucidates a fundamental question regarding the functional roles of transcription factors and Polycomb-mediated epigenetic mechanisms in transcriptional regulation.

scholarly journals Bach1 regulates self-renewal and impedes mesendodermal differentiation of human embryonic stem cells

2019 ◽  
Vol 5 (3) ◽  
pp. eaau7887 ◽  
Author(s):  
Xiangxiang Wei ◽  
Jieyu Guo ◽  
Qinhan Li ◽  
Qianqian Jia ◽  
Qing Jing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Gene Promoters ◽  
Lineage Specification ◽  
Self Renewal ◽  
Polycomb Repressive Complex 2 ◽  
Direct Target ◽  
Processing Protease

The transcription factor BTB and CNC homology 1 (Bach1) is expressed in the embryos of mice, but whether Bach1 regulates the self-renewal and early differentiation of human embryonic stem cells (hESCs) is unknown. We report that the deubiquitinase ubiquitin-specific processing protease 7 (Usp7) is a direct target of Bach1, that Bach1 interacts with Nanog, Sox2, and Oct4, and that Bach1 facilitates their deubiquitination and stabilization via the recruitment of Usp7, thereby maintaining stem cell identity and self-renewal. Bach1 also interacts with polycomb repressive complex 2 (PRC2) and represses mesendodermal gene expression by recruiting PRC2 to the genes’ promoters. The loss of Bach1 in hESCs promotes differentiation toward the mesendodermal germ layers by reducing the occupancy of EZH2 and H3K27me3 in mesendodermal gene promoters and by activating the Wnt/β-catenin and Nodal/Smad2/3 signaling pathways. Our study shows that Bach1 is a key determinant of pluripotency, self-renewal, and lineage specification in hESCs.

scholarly journals Functional impact of cancer-associated cohesin variants on gene expression and cellular identity

Genetics ◽  
2021 ◽  
Author(s):  
Natalie L Rittenhouse ◽  
Zachary M Carico ◽  
Ying Frances Liu ◽  
Holden C Stefan ◽  
Nicole L Arruda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Chromosome Structure ◽  
Embryonic Stem ◽  
Sequence Variants ◽  
Dna Loops ◽  
Murine Embryonic Stem Cells ◽  
Recurrent Mutations ◽  
Cellular Identity

Abstract Cohesin is a ring-shaped protein complex that controls dynamic chromosome structure. Cohesin activity is important for a variety of biological processes, including formation of DNA loops that regulate gene expression. The precise mechanisms by which cohesin shapes local chromosome structure and gene expression are not fully understood. Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, we utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells and investigate their molecular and cellular consequences. Some of the cohesin variants tested caused changes to transcription, including altered expression of gene encoding lineage-specifying developmental regulators. Altered gene expression was also observed at insulated neighborhoods, where cohesin-mediated DNA loops constrain potential interactions between genes and enhancers. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This study provides a functional comparison of cohesin variants found in cancer within an isogenic system, revealing the relative roles of various cohesin perturbations on gene expression and maintenance of cellular identity.

Effect of melatonin on mRNA expressions of transcription factors in murine embryonic stem cells

2011 ◽  
Vol 1385 ◽  
pp. 1-7 ◽  
Author(s):  
Yeong-Min Yoo ◽  
Eui-Man Jung ◽  
Kyung-Chul Choi ◽  
Eui-Bae Jeung
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Murine Embryonic Stem Cells

Pitx2c Modulates Cardiac-Specific Transcription Factors Networks in Differentiating Cardiomyocytes from Murine Embryonic Stem Cells

2011 ◽  
Vol 194 (5) ◽  
pp. 349-362 ◽  
Author(s):  
Estefanía Lozano-Velasco ◽  
Ana Chinchilla ◽  
Sergio Martínez-Fernández ◽  
Francisco Hernández-Torres ◽  
Francisco Navarro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Murine Embryonic Stem Cells

scholarly journals Endogenous retroviruses co-opted into divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells

2021 ◽  
Author(s):  
Stylianos Bakoulis ◽  
Robert Krautz ◽  
Nicolas Alcaraz ◽  
Marco Salvatore ◽  
Robin Andersson
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Transposable Elements ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Endogenous Retroviruses ◽  
Gene Promoters ◽  
Specific Regulation ◽  
Regulatory Landscape

Transcription factor binding to regulatory elements is the key process underlying gene regulation during cellular differentiation. Although the specific regulation of genes by transcription factors is generally conserved, regulatory elements themselves are associated with high evolutionary turnover, a process that has been attributed to transposable elements. However, it is unclear how frequent co-option of transposable elements into regulatory elements is and to which regulatory programs they contribute. Here, we report an in-depth characterization of the transposon-derived regulatory landscape of mouse embryonic stem cells. We demonstrate that a substantial number of endogenous retroviral elements are divergently transcribed into unstable RNAs, and that these elements contribute to a sizable proportion of active enhancers and gene promoters. We further show that transposon subfamilies contribute to specific regulatory programs through their enrichment of binding sites for transcription factors, shedding light on the formation of regulatory programs and the origins of regulatory elements.

Sign in / Sign up

Export Citation Format

Share Document