The nuclear periphery of embryonic stem cells is a transcriptionally permissive and repressive compartment
Author:
Luo Li12, Gassman Katherine L.1, Petell Lydia M.1, Wilson Christian L.13, Bewersdorf Joerg1, Shopland Lindsay S.1
Affiliation:
1. Institute for Molecular Biophysics, The Jackson Laboratory, Bar Harbor, ME 04609, USA 2. Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China 3. Department of Mathematics, University of Maine, Orono, ME 04469, USA
Abstract
Chromatin adapts a distinct structure and epigenetic state in embryonic stem cells (ESCs), but how chromatin is three-dimensionally organized within the ESC nucleus is poorly understood. Because nuclear location can influence gene expression, we examined the nuclear distributions of chromatin with key epigenetic marks in ESC nuclei. We focused on chromatin at the nuclear periphery, a compartment that represses some but not all associated genes and accumulates facultative heterochromatin in differentiated cells. Using a quantitative, cytological approach, we measured the nuclear distributions of genes in undifferentiated mouse ESCs according to epigenetic state and transcriptional activity. We found that trimethyl histone H3 lysine 27 (H3K27-Me3), which marks repressed gene promoters, is enriched at the ESC nuclear periphery. In addition, this compartment contains 10-15% of chromatin with active epigenetic marks and hundreds of transcription sites. Surprisingly, comparisons with differentiated cell types revealed similar nuclear distributions of active chromatin. By contrast, H3K27-Me3 was less concentrated at the nuclear peripheries of differentiated cells. These findings demonstrate that the nuclear periphery is an epigenetically dynamic compartment that might be distinctly marked in pluripotent ESCs. In addition, our data indicate that the nuclear peripheries of multiple cell types can contain a significant fraction of both active and repressed genes.
Publisher
The Company of Biologists
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