Insights into the Establishment of Chromatin States in Pluripotent Cells from Studies of X Inactivation.
Animal development entails the sequential and coordinated specialization of cells. During cell differentiation, transcription factors, cell signaling pathways, and chromatin-associated protein complexes cooperate in regulating the expression of a large number of genes. Here, we review the present understanding of the establishment of chromatin states by focusing on X chromosome inactivation (XCI) as a model for facultative heterochromatin formation in female embryonic cells. The inactive X chromosome is large enough to be investigated by biochemical and microscopy techniques. In addition, the ability to compare the inactivated chromatin to the active X in male cells enables us to differentiate events specific to gene silencing during XCI from gene regulatory effects from changing pathways in the same cell. Findings in XCI are useful as blueprints for investigation of the action of epigenetic pathways in differentiation and lineage commitment. We summarize recent studies that have identified factors that are critical for chromosome-wide gene repression in XCI, and we discuss their implications for epigenetic regulation in pluripotent cells of the early embryo.
Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Sciences Program, University of Zurich, 8049 Zurich, Switzerland.
Andreas
A
Postlmayr
Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland. Electronic address: awutz@ethz.ch.
Anton
A
Wutz
D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D003584:Cytological Techniques; D006801:Humans; D008853:Microscopy; D039904:Pluripotent Stem Cells / Q000502:physiology*; D049951:X Chromosome Inactivation
D002843:Chromatin
animal development; chromatin; gene regulation; noncoding RNA; pluripotent stem cell