TY - JOUR
T1 - REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis
AU - Ballas, Nurit
AU - Grunseich, Christopher
AU - Lu, Diane D.
AU - Speh, Joan C.
AU - Mandel, Gail
N1 - Funding Information:
We are grateful to Dr. Freda Miller for sharing her expertise on the isolation and culture of cortical progenitors, to Dr. Sally Temple for advice and expertise in sorting progenitors for LeX, and to Dr. Tom Rosenquist for providing mouse ES cells and advice on their culturing conditions. We also thank Dr. Andrew Brooks, ChinYi Chu, and John Hover for computational support. G.M. is an Investigator of the Howard Hughes Medical Institute. C.G. and D.D.L. received support from the Howard Hughes Medical Institute as physician scientist and summer student, respectively. The research was also supported by a grant from the National Institutes of Health to G.M.
PY - 2005/5/20
Y1 - 2005/5/20
N2 - Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its corepressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.
AB - Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its corepressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.
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U2 - 10.1016/j.cell.2005.03.013
DO - 10.1016/j.cell.2005.03.013
M3 - Article
C2 - 15907476
AN - SCOPUS:19344378337
SN - 0092-8674
VL - 121
SP - 645
EP - 657
JO - Cell
JF - Cell
IS - 4
ER -