Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation

  1. Jonghwan Kim1,2,3
  1. 1Department of Molecular Biosciences,
  2. 2Institute for Cellular and Molecular Biology,
  3. 3Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas 78712, USA
  1. Corresponding authors: jonghwankim{at}mail.utexas.edu; haleytucker{at}austin.utexas.edu

Abstract

Despite their origin from the inner cell mass, embryonic stem (ES) cells undergo differentiation to the trophectoderm (TE) lineage by repression of the ES cell master regulator Oct4 or activation of the TE master regulator Caudal-type homeobox 2 (Cdx2). In contrast to the in-depth studies of ES cell self-renewal and pluripotency, few TE-specific regulators have been identified, thereby limiting our understanding of mechanisms underlying the first cell fate decision. Here we show that up-regulation and nuclear entry of AT-rich interactive domain 3a (Arid3a) drives TE-like transcriptional programs in ES cells, maintains trophoblast stem (TS) cell self-renewal, and promotes further trophoblastic differentiation both upstream and independent of Cdx2. Accordingly, Arid3a−/− mouse post-implantation placental development is severely impaired, resulting in early embryonic death. We provide evidence that Arid3a directly activates TE-specific and trophoblast lineage-specific genes while directly repressing pluripotency genes via differential regulation of epigenetic acetylation or deacetylation. Our results identify Arid3a as a critical regulator of TE and placental development through execution of the commitment and differentiation phases of the first cell fate decision.

Keywords

Footnotes

  • Received June 10, 2014.
  • Accepted September 17, 2014.

This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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