Distinct profiles of REST interactions with its target genes at different stages of neuronal development.
Differentiation of pluripotent embryonic stem (ES) cells through multipotent neural stem (NS) cells into differentiated neurons is accompanied by wholesale changes in transcriptional programs. One factor that is present at all three stages and a key to neuronal differentiation is the RE1-silencing transcription factor (REST/NRSF). Here, we have used a novel chromatin immunoprecipitation-based cloning strategy (SACHI) to identify 89 REST target genes in ES cells, embryonic hippocampal NS cells and mature hippocampus. The gene products are involved in all aspects of neuronal function, especially neuronal differentiation, axonal growth, vesicular transport and release, and ionic conductance. Most target genes are silent or expressed at low levels in ES and NS cells, but are expressed at much higher levels in hippocampus. These data indicate that the REST regulon is specific to each developmental stage and support the notion that REST plays distinct roles in regulating gene expression in pluripotent ES cells, multipotent NS cells, and mature neurons.
Sun
Yuh-Man
YM
School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom. y.sun@bmb.leeds.ac.uk
Greenway
Deborah J
DJ
Johnson
Rory
R
Street
Miyoko
M
Belyaev
Nikolai D
ND
Deuchars
Jim
J
Bee
Thomas
T
Wilde
Sandra
S
Buckley
Noel J
NJ
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure; D003001:Cloning, Molecular; D016384:Consensus Sequence; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
D002843:Chromatin; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor