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UTF1 is a chromatin-associated protein involved in ES cell differentiation

¹ Developmental Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9750 AA Haren, Netherlands
² Department of Pathology, ³ Department of Cell Biology and Genetics, and ⁴ Department of Radiation Oncology, Erasmus MC, 3000 CA Rotterdam, Netherlands
⁵ Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8655, Japan
⁶ Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan

Correspondence to Bart J.L. Eggen: b.j.l.eggen{at}rug.nl

Embryonic stem (ES) cells are able to grow indefinitely (self-renewal) and have the potential to differentiate into all adult cell types (pluripotency). The regulatory network that controls pluripotency is well characterized, whereas the molecular basis for the transition from self-renewal to the differentiation of ES cells is much less understood, although dynamic epigenetic gene silencing and chromatin compaction are clearly implicated. In this study, we report that UTF1 (undifferentiated embryonic cell transcription factor 1) is involved in ES cell differentiation. Knockdown of UTF1 in ES and carcinoma cells resulted in a substantial delay or block in differentiation. Further analysis using fluorescence recovery after photobleaching assays, subnuclear fractionations, and reporter assays revealed that UTF1 is a stably chromatin-associated transcriptional repressor protein with a dynamic behavior similar to core histones. An N-terminal Myb/SANT domain and a C-terminal domain containing a putative leucine zipper are required for these properties of UTF1. These data demonstrate that UTF1 is a strongly chromatin-associated protein involved in the initiation of ES cell differentiation.

V. van den Boom's present address is Department of Cell Biology, Section of Stem Cell Biology, University Medical Centre Groningen, 9700 RB Groningen, Netherlands.

Abbreviations used in this paper: BMP, bone morphogenetic protein; BRE, BMP-responsive element; CD, conserved domain; EB, embryoid body; EC, embryonic carcinoma; eGFP, enhanced GFP; ES, embryonic stem; HDAC1, histone deacetylase 1; KD, knockdown; mUTF1, mouse UTF1; PcG, Polycomb group; SBE, Smad-binding element; TK, thymidine kinase; UTF1, undifferentiated embryonic cell transcription factor 1; wt, wild type.

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