This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cotterman, R. Articles by Knoepfler, P. S. Search for Related Content PubMed PubMed Citation Articles by Cotterman, R. Articles by Knoepfler, P. S.

N-Myc Regulates a Widespread Euchromatic Program in the Human Genome Partially Independent of Its Role as a Classical Transcription Factor

Departments of ¹ Cell Biology and Human Anatomy and ² Pharmacology, University of California Davis School of Medicine, Davis, California; ³ Institute of Pediatric Regenerative Medicine, ⁴ Shriners Hospital for Children Northern California, Sacramento, California; ⁵ Department of Biology and ⁶ Bioinformatics Program, University of Memphis, Memphis, Tennessee

Requests for reprints: Paul S. Knoepfler, University of California Davis, 1 Shields Avenue, Tupper Hall 3301, Davis, CA 95616. Phone: 916-453-2289; Fax: 916-453-2288; E-mail: knoepfler{at}ucdavis.edu.

Key Words: Myc • global chromatin • intergenic • neuroblastoma • stem cell • iPS

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. [Cancer Res 2008;68(23):9654–62]

This article has been cited by other articles:

				N. V. Varlakhanova and P. S. Knoepfler Acting Locally and Globally: Myc's Ever-Expanding Roles on Chromatin Cancer Res., October 1, 2009; 69(19): 7487 - 7490. [Abstract] [Full Text] [PDF]