Transcriptional competence in pluripotency

Abstract

Embryonic stem (ES) cells possess a globally open, decondensed chromatin structure that, together with trans-acting factors, supports transcriptional competence of developmentally regulated genes. However, our understanding of the mechanisms that establish transcriptional competence of specific genes is limited. In this issue of Genes & Development, Xu and colleagues (pp. 2824-2838) show that tissue-specific enhancers are actively marked by an unmethylated window in ES cells and induced pluripotent stem (iPS) cells. They propose a model and present supporting evidence to demonstrate the active involvement of pioneer transcription factors in this process. This work marks an important step toward the understanding of the mechanisms that define and maintain pluripotency, and calls for the identification of the factors that participate in the establishment of transcriptional competence in pluripotent cells.

Figure 1.

Epigenetic enhancer regulation during differentiation/development. (A) Enhancer and promoter modifications of a pluripotency-related gene and a tissue-specific gene in pluripotent stem cells. (Right) Chromatin is open and readily accessible in these cells, and pioneer factors can gain access to their binding sites easily and maintain an unmethylated window at tissue-specific gene enhancers. A typical pluripotency-related gene enhancer such as Oct4 contains less CpG methylation in pluripotent cells in comparison with differentiated cells (Hattori et al. 2004). (B) In multipotent progenitor cells, chromatin accessibility is more restricted and pluripotency gene expression is shut down. Enhancer methylation status of pluripotency-related genes is not clear. Chromatin remodelers and other lineage-specific factors may bind the tissue-specific enhancer and keep the gene in a poised state. (C) In differentiated cells, chromatin is more tightly packed and pluripotency genes are actively repressed. However, at tissue-specific gene enhancers, the chromatin is kept in an open conformation due to active marking by transcription factors. Binding of tissue-specific transcription factors to tissue-specific enhancers ensures proper transcription.