title: N-Myc and GCN5 regulate significantly overlapping transcriptional programs in neural stem cells.
abstract: Here we examine the functions of the Myc cofactor and histone acetyltransferase, GCN5/KAT2A, in neural stem and precursor cells (NSC) using a conditional knockout approach driven by nestin-cre. Mice with GCN5-deficient NSC exhibit a 25% reduction in brain mass with a microcephaly phenotype similar to that observed in nestin-cre driven knockouts of c- or N-myc. In addition, the loss of GCN5 inhibits precursor cell proliferation and reduces their populations in vivo, as does loss of N-myc. Gene expression analysis indicates that about one-sixth of genes whose expression is affected by loss of GCN5 are also affected in the same manner by loss of N-myc. These findings strongly support the notion that GCN5 protein is a key N-Myc transcriptional cofactor in NSC, but are also consistent with recruitment of GCN5 by other transcription factors and the use by N-Myc of other histone acetyltransferases. Putative N-Myc/GCN5 coregulated transcriptional pathways include cell metabolism, cell cycle, chromatin, and neuron projection morphogenesis genes. GCN5 is also required for maintenance of histone acetylation both at its putative specific target genes and at Myc targets. Thus, we have defined an important role for GCN5 in NSC and provided evidence that GCN5 is an important Myc transcriptional cofactor in vivo.
authors: Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, California, United States of America.
authors: Verónica
authors: V
authors: Martínez-Cerdeño
authors: Jessica M
authors: JM
authors: Lemen
authors: Vanessa
authors: V
authors: Chan
authors: Alice
authors: A
authors: Wey
authors: Wenchu
authors: W
authors: Lin
authors: Sharon R
authors: SR
authors: Dent
authors: Paul S
authors: PS
authors: Knoepfler
mesh_terms: D000107:Acetylation; D000818:Animals; D047369:Chromatin Immunoprecipitation; D005260:Female; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D006657:Histones; D016271:Proto-Oncogene Proteins c-myc; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor