scholarly journals Modeling the relative relationship of transcription factor binding and histone modifications to gene expression levels in mouse embryonic stem cells

2011 ◽  
Vol 40 (2) ◽  
pp. 553-568 ◽  
Author(s):  
Chao Cheng ◽  
Mark Gerstein
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Histone Modifications ◽  
Embryonic Stem ◽  
Expression Levels ◽  
Factor Binding ◽  
Relationship Of ◽  
Gene Expression Levels

scholarly journals Methylation QTLs Are Associated with Coordinated Changes in Transcription Factor Binding, Histone Modifications, and Gene Expression Levels

PLoS Genetics ◽  
2014 ◽  
Vol 10 (9) ◽  
pp. e1004663 ◽  
Author(s):  
Nicholas E. Banovich ◽  
Xun Lan ◽  
Graham McVicker ◽  
Bryce van de Geijn ◽  
Jacob F. Degner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Histone Modifications ◽  
Transcription Factor Binding ◽  
Expression Levels ◽  
Factor Binding ◽  
Gene Expression Levels

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 Dynamics of gene expression with positive feedback to histone modifications at bivalent domains

2018 ◽  
Vol 32 (07) ◽  
pp. 1850075
Author(s):  
Rongsheng Huang ◽  
Jinzhi Lei
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Histone Modification ◽  
Histone Modifications ◽  
Positive Feedback ◽  
State Transition ◽  
Embryonic Stem ◽  
Cell Cycles ◽  
Histone Marks

Experiments have shown that in embryonic stem cells, the promoters of many lineage-control genes contain “bivalent domains”, within which the nucleosomes possess both active (H3K4me3) and repressive (H3K27me3) marks. Such bivalent modifications play important roles in maintaining pluripotency in embryonic stem cells. Here, to investigate gene expression dynamics when there are regulations in bivalent histone modifications and random partition in cell divisions, we study how positive feedback to histone methylation/demethylation controls the transition dynamics of the histone modification patterns along with cell cycles. We constructed a computational model that includes dynamics of histone marks, three-stage chromatin state transitions, transcription and translation, feedbacks from protein product to enzymes to regulate the addition and removal of histone marks, and the inheritance of nucleosome state between cell cycles. The model reveals how dynamics of both nucleosome state transition and gene expression are dependent on the enzyme activities and feedback regulations. Results show that the combination of stochastic histone modification at each cell division and the deterministic feedback regulation work together to adjust the dynamics of chromatin state transition in stem cell regenerations.

scholarly journals Quantitative Transcription Factor Analysis of Undifferentiated Single Human Embryonic Stem Cells

2009 ◽  
Vol 55 (12) ◽  
pp. 2162-2170 ◽  
Author(s):  
Anders Ståhlberg ◽  
Martin Bengtsson ◽  
Martin Hemberg ◽  
Henrik Semb
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Cell Line ◽  
Human Embryonic Stem Cells ◽  
Single Cells ◽  
Embryonic Stem ◽  
Measurement Noise ◽  
Sox2 Expression

Abstract Background: Human embryonic stem cells (hESCs) require expression of transcription factor genes POU5F1 (POU class 5 homeobox 1), NANOG (Nanog homeobox), and SOX2 [SRY (sex determining region Y)-box 2] to maintain their capacity for self-renewal and pluripotency. Because of the heterogeneous nature of cell populations, it is desirable to study the gene regulation in single cells. Large and potentially important fluctuations in a few cells cannot be detected at the population scale with microarrays or sequencing technologies. We used single-cell gene expression profiling to study cell heterogeneity in hESCs. Methods: We collected 47 single hESCs from cell line SA121 manually by glass capillaries and 57 single hESCs from cell line HUES3 by flow cytometry. Single hESCs were lysed and reverse-transcribed. Reverse-transcription quantitative real-time PCR was then used to measure the expression POU5F1, NANOG, SOX2, and the inhibitor of DNA binding genes ID1, ID2, and ID3. A quantitative noise model was used to remove measurement noise when pairwise correlations were estimated. Results: The numbers of transcripts per cell varied >100-fold between cells and showed lognormal features. POU5F1 expression positively correlated with ID1 and ID3 expression (P < 0.05) but not with NANOG or SOX2 expression. When we accounted for measurement noise, SOX2 expression was also correlated with ID1, ID2, and NANOG expression (P < 0.05). Conclusions: We demonstrate an accurate method for transcription profiling of individual hESCs. Cell-to-cell variability is large and is at least partly nonrandom because we observed correlations between core transcription factors. High fluctuations in gene expression may explain why individual cells in a seemingly undifferentiated cell population have different susceptibilities for inductive cues.

scholarly journals Rewiring of transcription factor binding in differentiating human embryonic stem cells is constrained by DNA sequence repeat symmetry

2018 ◽  
Author(s):  
Matan Goldshtein ◽  
David B. Lukatsky
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Dna Binding ◽  
Dna Sequence ◽  
Histone Modifications ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Sequence Repeat ◽  
Dna Repeat

ABSTRACTWe analyze design principles of transcription factor (TF) recognition by genomic DNA in differentiating human embryonic stem cells for 36 TFs and five histone modifications in four developmental layers, using the data recently measured by Tsankov et al. This analysis reveals that DNA sequence repeat symmetry plays a central role in defining TF-DNA binding preferences across different developmental layers. In particular, we find that different TFs bind similar symmetry patterns within a given developmental layer. While the TF cluster content undergoes modifications upon transitions between different developmental layers, most TFs possess dominant preferences for similar DNA repeat symmetry types. Histone modifications also exhibit strong preferences for similar DNA repeat symmetry patterns, with the symmetry strength differentiating between different histone modifications. Overall, our findings show that despite the enormous sequence complexity of the TF-DNA binding landscape in differentiating human embryonic stem cells, this landscape can be quantitatively characterized in simple terms, using the notion of DNA sequence repeat symmetry.

scholarly journals Transcription Factor Binding in Embryonic Stem Cells Is Constrained by DNA Sequence Repeat Symmetry

2020 ◽  
Vol 118 (8) ◽  
pp. 2015-2026 ◽  
Author(s):  
Matan Goldshtein ◽  
Meir Mellul ◽  
Gai Deutch ◽  
Masahiko Imashimizu ◽  
Koh Takeuchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Dna Sequence ◽  
Embryonic Stem ◽  
Transcription Factor Binding ◽  
Sequence Repeat ◽  
Factor Binding
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