Role of the epigenetic regulator HP1λ in the control of embryonic stem cell properties

Abstract

The unique properties of embryonic stem cells (ESC) rely on long-lasting self-renewal and their ability to switch in all adult cell type programs. Recent advances have shown that regulations at the chromatin level sustain both ESC properties along with transcription factors. We have focused our interest on the epigenetic modulator HP1λ (Heterochromatin Protein 1, isoform c) that binds histones H3 methylated at lysine 9 (meH3K9) and is highly plastic in its distribution and association with the transcriptional regulation of specific genes during cell fate transitions. These characteristics of HP1λ make it a good candidate to sustain the ESC flexibility required for rapid program changes during differentiation n. Using RNA interference,we describe the functional role of HP1λ in mouse ESC. The analysis of HP1λ deprived cells in proliferative and in various differentiating conditions was performed combining functional assays with molecular approaches (RT-qPCR, microarray). We show that HP1λ deprivation slows down the cell cycle of ESC and decreases their resistance to dif ferentiating conditions,rendering the cells poised to differentiate. In addition, HP1λ depletion hampers the differentiation to the endoderm as compared with the differentiation to the neurectoderm or the mesoderm. Altogether, our results reveal the role of HP1λ in ESC self-renewal and in the balance between the pluripotent and the differentiation programs. © 2010 Caillier et al.