Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/133506
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Type: | Journal article |
Title: | TFAP2C regulates transcription in human naive pluripotency by opening enhancers |
Author: | Pastor, W.A. Liu, W. Chen, D. Ho, J. Kim, R. Hunt, T.J. Lukianchikov, A. Liu, X. Polo, J.M. Jacobsen, S.E. Clark, A.T. |
Citation: | Nature Cell Biology, 2018; 20(5):553-564 |
Publisher: | Nature Research |
Issue Date: | 2018 |
ISSN: | 1465-7392 1476-4679 |
Statement of Responsibility: | William A. Pastor, Wanlu Liu, Di Chen, Jamie Ho, Rachel Kim, Timothy J. Hunt, Anastasia Lukianchikov, Xiaodong Liu, Jose M. Polo, Steven E. Jacobsen, Amander T. Clark |
Abstract: | Naive and primed pluripotent human embryonic stem cells bear transcriptional similarity to pre- and post-implantation epiblast and thus constitute a developmental model for understanding the pluripotent stages in human embryo development. To identify new transcription factors that differentially regulate the unique pluripotent stages, we mapped open chromatin using ATACseq and found enrichment of the activator protein-2 (AP2) transcription factor binding motif at naive-specific open chromatin. We determined that the AP2 family member TFAP2C is upregulated during primed to naive reversion and becomes widespread at naive-specific enhancers. TFAP2C functions to maintain pluripotency and repress neuroectodermal differentiation during the transition from primed to naive by facilitating the opening of enhancers proximal to pluripotency factors. Additionally, we identify a previously undiscovered naive-specific POU5F1 (OCT4) enhancer enriched for TFAP2C binding. Taken together, TFAP2C establishes and maintains naive human pluripotency and regulates OCT4 expression by mechanisms that are distinct from mouse. |
Keywords: | Cells, Cultured Chromatin Animals Humans Mice Signal Transduction Chromatin Assembly and Disassembly Species Specificity Transcription, Genetic Gene Expression Regulation, Developmental Binding Sites Protein Binding Cell Lineage Phenotype Transcription Factor AP-2 Octamer Transcription Factor-3 Enhancer Elements, Genetic Nucleotide Motifs Human Embryonic Stem Cells Mouse Embryonic Stem Cells |
Rights: | © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved |
DOI: | 10.1038/s41556-018-0089-0 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1104560 |
Published version: | http://dx.doi.org/10.1038/s41556-018-0089-0 |
Appears in Collections: | Molecular and Biomedical Science publications |
Files in This Item:
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hdl_133506.pdf | Accepted version | 2.27 MB | Adobe PDF | View/Open |
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