TFAP2C regulates transcription in human naive pluripotency by opening enhancers

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

Research output: Contribution to journalArticleResearchpeer-review

108 Citations (Scopus)

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 ATAC-seq 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.

Original languageEnglish
Pages (from-to)553-564
Number of pages12
JournalNature Cell Biology
Volume20
Issue number5
DOIs
Publication statusPublished - 1 May 2018

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