Adaption by Rewiring Epigenetic Landscapes

Abstract

Embryonic stem cells (ESCs) generally rely on repressive histone modifications to silence retrotransposons, rather than DNA methylation as in differentiated cells. In this issue of Cell Stem Cell, He et al. (2015) show that Daxx/Atrx repress transposons in ESCs devoid of 5mC, demonstrating dynamic reorganization of epigenetic networks and crosstalk between distinct repressive mechanisms to maintain transposon silencing.

Figure 1. DAXX-Centered Epigenetic Repression

(A) An abbreviated classification of transposable elements (TEs) in mice. Active members are shown in blue. LINE, long interspersed element; SINE, short interspersed element; ERV, endogenous retrovirus; MuLV, Murine Leukemia Virus; MuRRS, murine retrovirus-related sequence; IAP, intracisternal A-particle; ETn, early transposon; MuERV-L, murine endogenous retrovirus-L; MaLR, mammalian long terminal repeat transposon. (B) Wild-type ESCs (upper panel) use repressive histone marks of H3K9me2/3 and 5mC to silence TE and telomeres, in which the Daxx/Atrx/Suv39h1 binding seems attenuated. In TKO ESCs that lack 5mC (middle panel), enhanced Daxx/Atrx/Suv39h1 occupancy at retrotransposons and telomeres results in increased H3K9me3 levels and maintenance of TE silencing. Simultaneous loss of 5mC and Daxx (lower panel) leads to TE derepression and telomere dysfunction. Transcription levels are indicated by the color-coded arrows; a gray arrow signifies transcription inactivation and a green arrow signifies transcription activation.