TIF1β regulates the pluripotency of embryonic stem cells in a phosphorylation-dependent manner

Yasuhiro Seki, Akira Kurisaki, Kanako Watanabe-Susaki, Yoshiro Nakajima, Mio Nakanishi, Yoshikazu Arai, Kunio Shiota, Hiromu Sugino, Makoto Asashima

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Transcription networks composed of various transcriptional factors specifically expressed in undifferentiated embryonic stem (ES) cells have been implicated in the regulation of pluripotency in ES cells. However, the molecular mechanisms responsible for self-renewal, maintenance of pluripotency, and lineage specification during differentiation of ES cells are still unclear. The results of this study demonstrate that a phosphorylation-dependent chromatin relaxation factor, transcriptional intermediary factor-1β (TIF1β), is a unique regulator of the pluripotency of ES cells and regulates Oct3/4-dependent transcription in a phosphorylation-dependent manner. TIF1β is specifically phosphorylated in pluripotent mouse ES cells at the C-terminal serine 824, which has been previously shown to induce chromatin relaxation. Phosphorylated TIF1β is partially colocalized at the activated chromatin markers, and forms a complex with the pluripotency-specific transcription factor Oct3/4 and subunits of the switching defective/sucrose nonfermenting, ATP-dependent chromatin remodeling complex, Smarcad1, Brg-1, and BAF155, all of which are components of an ES-specific chromatin remodeling complex, esBAF. Phosphorylated TIF1β specifically induces ES cell-specific genes and enables prolonged maintenance of an undifferentiated state in mouse ES cells. Moreover, TIF1β regulates the reprogramming process of somatic cells in a phosphorylation-dependent manner. Our results suggest that TIF1β provides a phosphorylation-dependent, bidirectional platform for specific transcriptional factors and chromatin remodeling enzymes that regulate the cell differentiation process and the pluripotency of stem cells.

Original languageEnglish
Pages (from-to)10926-10931
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number24
DOIs
Publication statusPublished - 2010 Jun 15
Externally publishedYes

Keywords

  • Chromatin remodeling
  • Differentiation
  • esBAF
  • iPS cells
  • Oct3/4

ASJC Scopus subject areas

  • General

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    Seki, Y., Kurisaki, A., Watanabe-Susaki, K., Nakajima, Y., Nakanishi, M., Arai, Y., Shiota, K., Sugino, H., & Asashima, M. (2010). TIF1β regulates the pluripotency of embryonic stem cells in a phosphorylation-dependent manner. Proceedings of the National Academy of Sciences of the United States of America, 107(24), 10926-10931. https://doi.org/10.1073/pnas.0907601107