Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
Xist is required for X inactivation. To study the initiation of X inactivation, we have generated a full-length mouse Xist cDNA transgene and an inducible expression system facilitating controlled Xist expression in ES cells and differentiated cultures. In ES cells, transgenic Xist RNA was stable and caused long-range transcriptional repression in cis. Repression was reversible and dependent on continued Xist expression in ES cells and early ES cell differentiation. By 72 hr of differentiation, inactivation became irreversible and independent of Xist. Upon differentiation, autosomal transgenes did not effect counting, but transgenic Xist RNA induced late replication and histone H4 hypoacetylation. Xist had to be activated within 48 hr of differentiation to effect silencing, suggesting that reversible repression by Xist is a required initiation step that might occur during normal X inactivation in female cells.
2. "A BAC-Based Physical Map of the Major Autosomes of Drosophila melanogaster".
3. "Ultrastructural Continuity between Active and Repressed Chromatin".
4. "Mechanisms of Repression and De-Repression within Interphase Chromatin".
5. "Selective Gene De-Repression by De-Repressor RNA".
6. " Nuclear RNA Species Activate DNA Transcription within Chromatin".
7. "Oncogenes as Molecular Targets within Active Chromatin".
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