N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor.
Myc proteins have long been modeled to operate strictly as classic gene-specific transcription factors; however, we find that N-Myc has a robust role in the human genome in regulating global cellular euchromatin, including that of intergenic regions. Strikingly, 90% to 95% of the total genomic euchromatic marks histone H3 acetylated at lysine 9 and methylated at lysine 4 is N-Myc-dependent. However, Myc regulation of transcription, even of genes it directly binds and at which it is required for the maintenance of active chromatin, is generally weak. Thus, Myc has a much more potent ability to regulate large domains of euchromatin than to influence the transcription of individual genes. Overall, Myc regulation of chromatin in the human genome includes both specific genes, but also expansive genomic domains that invoke functions independent of a classic transcription factor. These findings support a new dual model for Myc chromatin function with important implications for the role of Myc in cancer and stem cell biology, including that of induced pluripotent stem cells.
Cotterman
Rebecca
R
Department of Cell Biology, University of California Davis School of Medicine, Davis, California 95616, USA.
Jin
Victor X
VX
Krig
Sheryl R
SR
Lemen
Jessica M
JM
Wey
Alice
A
Farnham
Peggy J
PJ
Knoepfler
Paul S
PS
D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D024721:E-Box Elements; D016259:Genes, myc; D015894:Genome, Human; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D019076:Transgenes
D002843:Chromatin; D006657:Histones; D016271:Proto-Oncogene Proteins c-myc