scholarly journals MMTR/Dmap1 Sets the Stage for Early Lineage Commitment of Embryonic Stem Cells by Crosstalk with PcG Proteins

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1190
Author(s):  
Young Jin Lee ◽  
Seung Han Son ◽  
Chang Su Lim ◽  
Min Young Kim ◽  
Si Woo Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcriptional Regulation ◽  
Embryonic Stem Cells ◽  
Chromatin Remodeling ◽  
Embryonic Stem ◽  
Lineage Commitment ◽  
Regulation Mechanism ◽  
Mouse Escs ◽  
Nucleosome Remodeling

Chromatin remodeling, including histone modification, chromatin (un)folding, and nucleosome remodeling, is a significant transcriptional regulation mechanism. By these epigenetic modifications, transcription factors and their regulators are recruited to the promoters of target genes, and thus gene expression is controlled through either transcriptional activation or repression. The Mat1-mediated transcriptional repressor (MMTR)/DNA methyltransferase 1 (DNMT1)-associated protein (Dmap1) is a transcription corepressor involved in chromatin remodeling, cell cycle regulation, DNA double-strand break repair, and tumor suppression. The Tip60-p400 complex proteins, including MMTR/Dmap1, interact with the oncogene Myc in embryonic stem cells (ESCs). These proteins interplay with the stem cell-related proteome networks and regulate gene expressions. However, the detailed mechanisms of their functions are unknown. Here, we show that MMTR/Dmap1, along with other Tip60-p400 complex proteins, bind the promoters of differentiation commitment genes in mouse ESCs. Hence, MMTR/Dmap1 controls gene expression alterations during differentiation. Furthermore, we propose a novel mechanism of MMTR/Dmap1 function in early stage lineage commitment of mouse ESCs by crosstalk with the polycomb group (PcG) proteins. The complex controls histone mark bivalency and transcriptional poising of commitment genes. Taken together, our comprehensive findings will help better understand the MMTR/Dmap1-mediated transcriptional regulation in ESCs and other cell types.

scholarly journals Mammalian SWI/SNF Chromatin Remodeling Complexes in Embryonic Stem Cells: Regulating the Balance Between Pluripotency and Differentiation

2021 ◽  
Vol 8 ◽  
Author(s):  
Ying Ye ◽  
Xi Chen ◽  
Wensheng Zhang
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Self Renewal ◽  
Baf Complex ◽  
Chromatin Remodeling Complexes

The unique capability of embryonic stem cells (ESCs) to maintain and adjust the equilibrium between self-renewal and multi-lineage cellular differentiation contributes indispensably to the integrity of all developmental processes, leading to the advent of an organism in its adult form. The ESC fate decision to favor self-renewal or differentiation into specific cellular lineages largely depends on transcriptome modulations through gene expression regulations. Chromatin remodeling complexes play instrumental roles to promote chromatin structural changes resulting in gene expression changes that are key to the ESC fate choices governing the equilibrium between pluripotency and differentiation. BAF (Brg/Brahma-associated factors) or mammalian SWI/SNF complexes employ energy generated by ATP hydrolysis to change chromatin states, thereby governing the accessibility of transcriptional regulators that ultimately affect transcriptome and cell fate. Interestingly, the requirement of BAF complex in self-renewal and differentiation of ESCs has been recently shown by genetic studies through gene expression modulations of various BAF components in ESCs, although the precise molecular mechanisms by which BAF complex influences ESC fate choice remain largely underexplored. This review surveys these recent progresses of BAF complex on ESC functions, with a focus on its role of conditioning the pluripotency and differentiation balance of ESCs. A discussion of the mechanistic bases underlying the genetic requirements for BAF in ESC biology as well as the outcomes of its interplays with key transcription factors or other chromatin remodelers in ESCs will be highlighted.

scholarly journals Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

2016 ◽  
Author(s):  
Stefan Semrau ◽  
Johanna Goldmann ◽  
Magali Soumillon ◽  
Tarjei S. Mikkelsen ◽  
Rudolf Jaenisch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Single Cell ◽  
Embryonic Stem ◽  
Lineage Commitment ◽  
Single Cell Level ◽  
Cell Level ◽  
Expression Variability ◽  
Gene Expression Heterogeneity

ABSTRACTGene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measured the gene expression dynamics of retinoic acid driven mESC differentiation using an unbiased single-cell transcriptomics approach. We found that the exit from pluripotency marks the start of a lineage bifurcation as well as a transient phase of susceptibility to lineage specifying signals. Our study revealed several transcriptional signatures of this phase, including a sharp increase of gene expression variability. Importantly, we observed a handover between two classes of transcription factors. The early-expressed class has potential roles in lineage biasing, the late-expressed class in lineage commitment. In summary, we provide a comprehensive analysis of lineage commitment at the single cell level, a potential stepping stone to improved lineage control through timing of differentiation cues.

scholarly journals Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development

2017 ◽  
Vol 114 (52) ◽  
pp. E11180-E11189 ◽  
Author(s):  
Kesavan Meganathan ◽  
Emily M. A. Lewis ◽  
Paul Gontarz ◽  
Shaopeng Liu ◽  
Edouard G. Stanley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Chromatin Remodeling ◽  
Human Embryonic Stem Cells ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Molecular Networks ◽  
Cortical Interneurons

Cortical interneurons (cINs) modulate excitatory neuronal activity by providing local inhibition. During fetal development, several cIN subtypes derive from the medial ganglionic eminence (MGE), a transient ventral telencephalic structure. While altered cIN development contributes to neurodevelopmental disorders, the inaccessibility of human fetal brain tissue during development has hampered efforts to define molecular networks controlling this process. Here, we modified protocols for directed differentiation of human embryonic stem cells, obtaining efficient, accelerated production of MGE-like progenitors and MGE-derived cIN subtypes with the expected electrophysiological properties. We defined transcriptome changes accompanying this process and integrated these data with direct transcriptional targets of NKX2-1, a transcription factor controlling MGE specification. This analysis defined NKX2-1–associated genes with enriched expression during MGE specification and cIN differentiation, including known and previously unreported transcription factor targets with likely roles in MGE specification, and other target classes regulating cIN migration and function. NKX2-1–associated peaks were enriched for consensus binding motifs for NKX2-1, LHX, and SOX transcription factors, suggesting roles in coregulating MGE gene expression. Among the NKX2-1 direct target genes with cIN-enriched expression was CHD2, which encodes a chromatin remodeling protein mutated to cause human epilepsies. Accordingly, CHD2 deficiency impaired cIN specification and altered later electrophysiological function, while CHD2 coassociated with NKX2-1 at cis-regulatory elements and was required for their transactivation by NKX2-1 in MGE-like progenitors. This analysis identified several aspects of gene-regulatory networks underlying human MGE specification and suggested mechanisms by which NKX2-1 acts with chromatin remodeling activities to regulate gene expression programs underlying cIN development.

Ethanol alters cell cycle gene expression in human embryonic stem cells

2016 ◽  
Vol 01 (03) ◽  
pp. 201-208 ◽  
Author(s):  
Malini Krishnamoorthy ◽  
Brian Gerwe ◽  
Jamie Heimburg-Molinaro ◽  
Rachel Nash ◽  
Jagan Arumugham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Cycle Gene ◽  
Cell Cycle Gene Expression

scholarly journals The Trends in Global Gene Expression in Mouse Embryonic Stem Cells During Spaceflight

2019 ◽  
Vol 10 ◽  
Author(s):  
Lili An ◽  
Yanming Li ◽  
Yingjun Fan ◽  
Ning He ◽  
Fanlei Ran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Global Gene Expression ◽  
Mouse Embryonic Stem Cells

3076 – FINE-TUNING GENE EXPRESSION BY CRISPRA IN MOUSE EMBRYONIC STEM CELLS FOR SPECIFIC TISSUE INDUCTION

2020 ◽  
Vol 88 ◽  
pp. S62
Author(s):  
Luis Galán Palma ◽  
Roshana Thambyrajah ◽  
Antonella Fidanza ◽  
Lesley Forrester ◽  
Pablo Menéndez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Fine Tuning ◽  
Specific Tissue

Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells

1994 ◽  
Vol 14 (5) ◽  
pp. 3108-3114
Author(s):  
M H Baron ◽  
S M Farrington
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Cultured Cells ◽  
Globin Gene ◽  
Embryonic Stem ◽  
Targeted Mutagenesis ◽  
Erythroid Cell ◽  
Erythroid Cells

The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.

scholarly journals Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells

FEBS Letters ◽  
2017 ◽  
Vol 591 (18) ◽  
pp. 2879-2889
Author(s):  
Yuki Saito ◽  
Akira Kunitomi ◽  
Tomohisa Seki ◽  
Shugo Tohyama ◽  
Dai Kusumoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem
Sign in / Sign up

Export Citation Format

Share Document