Selective influence of Sox2 on
            POU
            transcription factor binding in embryonic and neural stem cells

AbstractChanges in gene regulation have been shown to contribute to phenotypic differences between closely related species, most notably in primates. It is likely that a subset of inter-species regulatory differences can be explained by changes in chromatin accessibility and transcription factor binding, yet there is a paucity of comparative data sets with which to investigate this. Using ATAC-seq, we profiled genome-wide chromatin accessibility in a matched set of 6 human and 6 chimpanzee (Pan troglodytes, our closest living relative) induced pluripotent stem cells from which we have previously collected gene expression data. We examined chromatin accessibility patterns near 20,745 orthologous transcriptions start sites and used a footprinting algorithm to predict transcription factor binding activity in each species. We found that the majority of chromatin accessibility patterns and transcription factor activity are conserved between these two closely related species. Interestingly, interspecies divergence in chromatin accessibility and transcription factor binding in pluripotent cells appear to contribute not to differences in the pluripotent state, but to downstream developmental processes. Put together, our findings suggest that the pluripotent state is extremely stable and potentially subject to stronger evolutionary constraint than other somatic tissues.

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Predicting gene expression level by the transcription factor binding signals in human embryonic stem cells

Biosystems ◽

10.1016/j.biosystems.2016.08.011 ◽

2016 ◽

Vol 150 ◽

pp. 92-98 ◽

Cited By ~ 4

Author(s):

Lu-Qiang Zhang ◽

Qian-Zhong Li ◽

Wen-Xia Su ◽

Wen Jin

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Transcription Factor ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Transcription Factor Binding ◽

Gene Expression Level ◽

Expression Level ◽

Factor Binding

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A flexible repertoire of transcription factor binding sites and diversity threshold determines enhancer activity in embryonic stem cells

10.1101/2020.04.17.046664 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gurdeep Singh ◽

Shanelle Mullany ◽

Sakthi D Moorthy ◽

Richard Zhang ◽

Tahmid Mehdi ◽

...

Keyword(s):

Stem Cells ◽

Transcription Factor ◽

Embryonic Stem Cells ◽

Binding Sites ◽

Embryonic Stem ◽

Transcription Factor Binding Sites ◽

Transcription Factor Binding ◽

Enhancer Activity ◽

Factor Binding ◽

Master Regulators

ABSTRACTTranscriptional enhancers are critical for development, phenotype evolution and often mutated in disease contexts; however, even in well-studied cell types, the sequence code conferring enhancer activity remains unknown. We found genomic regions with conserved binding of multiple transcription factors in mouse and human embryonic stem cells (ESCs) contain on average 12.6 conserved transcription factor binding sites (TFBS). These TFBS are a diverse repertoire of 70 different sequences representing the binding sites of both known and novel ESC regulators. Remarkably, using a diverse set of TFBS from this repertoire was sufficient to construct short synthetic enhancers with activity comparable to native enhancers. Site directed mutagenesis of conserved TFBS in endogenous enhancers or TFBS deletion from synthetic sequences revealed a requirement for more than ten different TFBS. Furthermore, specific TFBS, including the OCT4:SOX2 co-motif, are dispensable, despite co-binding the OCT4, SOX2 and NANOG master regulators of pluripotency. These findings reveal a TFBS diversity threshold overrides the need for optimized regulatory grammar and individual TFBS that bind specific master regulators.

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