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

scholarly journals Transcription factor directed differentiation of human embryonic stem cells into the pancreatic endocrine lineage

Cell Research ◽  
2008 ◽  
Vol 18 (S1) ◽  
pp. S109-S109 ◽  
Author(s):  
Qing Le Liang ◽  
Xiao Xun Wang ◽  
Xiao Fei Yan ◽  
Li Jun Yang ◽  
Dong Qi Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Directed Differentiation

Human embryonic stem cells are characterized by distinct patterns of histone modifications in comparison with cells of feeder layer

2008 ◽  
Vol 2008 (Spring) ◽  
Author(s):  
Eva Bartova ◽  
Abdrea Harnicarova ◽  
Jana Krejci ◽  
Gabriela Galiova ◽  
Stanislav Kozubek
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Histone Modifications ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Feeder Layer

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 Erratum: WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells

Cell Research ◽  
2009 ◽  
Vol 19 (6) ◽  
pp. 796-796 ◽  
Author(s):  
Huiming Xu ◽  
Weicheng Wang ◽  
Chunliang Li ◽  
Hongyao Yu ◽  
Acong Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem

Properties of Human Embryonic Stem Cells and Their Differentiated Derivatives Depend on Nonhistone DNA-Binding HMGB1 and HMGB2 Proteins

2017 ◽  
Vol 26 (5) ◽  
pp. 328-340 ◽  
Author(s):  
Alireza Jian Bagherpoor ◽  
Dasa Dolezalova ◽  
Tomas Barta ◽  
Martin Kučírek ◽  
Soodabeh Abbasi Sani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Dna Binding ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem

scholarly journals Squelching of ETS2 Transactivation by POU5F1 Silences the Human Chorionic Gonadotropin CGA Subunit Gene in Human Choriocarcinoma and Embryonic Stem Cells

2012 ◽  
Vol 26 (5) ◽  
pp. 859-872 ◽  
Author(s):  
Rangan Gupta ◽  
Toshihiko Ezashi ◽  
R. Michael Roberts
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Binding Site ◽  
Chorionic Gonadotropin ◽  
Human Embryonic Stem Cells ◽  
Human Chorionic Gonadotropin ◽  
Promoter Activity ◽  
Embryonic Stem ◽  
Subunit Gene

Abstract The subunit genes encoding human chorionic gonadotropin, CGA, and CGB, are up-regulated in human trophoblast. However, they are effectively silenced in choriocarcinoma cells by ectopically expressed POU domain class 5 transcription factor 1 (POU5F1). Here we show that POU5F1 represses activity of the CGA promoter through its interactions with ETS2, a transcription factor required for both placental development and human chorionic gonadotropin subunit gene expression, by forming a complex that precludes ETS2 from interacting with the CGA promoter. Mutation of a POU5F1 binding site proximal to the ETS2 binding site does not alter the ability of POU5F1 to act as a repressor but causes a drop in basal promoter activity due to overlap with the binding site for DLX3. DLX3 has only a modest ability to raise basal CGA promoter activity, but its coexpression with ETS2 can up-regulate it 100-fold or more. The two factors form a complex, and both must bind to the promoter for the combination to be transcriptionally effective, a synergy compromised by POU5F1. Similarly, in human embryonic stem cells, which express ETS2 but not CGA, ETS2 does not occupy its binding site on the CGA promoter but is found instead as a soluble complex with POU5F1. When human embryonic stem cells differentiate in response to bone morphogenetic protein-4 and concentrations of POU5F1 fall and hCG and DLX3 rise, ETS2 then occupies its binding site on the CGA promoter. Hence, a squelching mechanism underpins the transcriptional silencing of CGA by POU5F1 and could have general relevance to how pluripotency is maintained and how the trophoblast lineage emerges from pluripotent precursor cells.

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