A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions.
The repressor element 1 (RE1) silencing transcription factor (REST) helps preserve the identity of nervous tissue by silencing neuronal genes in non-neural tissues. Moreover, in an epithelial model of tumorigenesis, loss of REST function is associated with loss of adhesion, suggesting the aberrant expression of REST-controlled genes encoding this property. To date, no adhesion molecules under REST control have been identified. Here, we used serial analysis of chromatin occupancy to perform genome-wide identification of REST-occupied target sequences (RE1 sites) in a kidney cell line. We discovered novel REST-binding motifs and found that the number of RE1 sites far exceeded previous estimates. A large family of targets encoding adhesion proteins was identified, as were genes encoding signature proteins of neuroendocrine tumors. Unexpectedly, genes considered exclusively non-neuronal also contained an RE1 motif and were expressed in neurons. This supports the model that REST binding is a critical determinant of neuronal phenotype.
Otto
Stefanie J
SJ
Howard Hughes Medical Institute, Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York 11794, USA.
McCorkle
Sean R
SR
Hover
John
J
Conaco
Cecilia
C
Han
Jong-Jin
JJ
Impey
Soren
S
Yochum
Gregory S
GS
Dunn
John J
JJ
Goodman
Richard H
RH
Mandel
Gail
G
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor