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

研究成果: Article査読

57 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)10926-10931
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
107
24
DOI
出版ステータスPublished - 2010 6 15
外部発表はい

ASJC Scopus subject areas

  • 一般

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