Fitzmartin, Kevin

Khan, Asadullah

Van Meter, Timothy E.

English

College of William & Mary: W&M Publish

W&M ScholarWorks Arts & Sciences Articles Arts and Sciences 2014 Aberrant myst4/brpf1 Signaling Misdirects Regional Neurogenesis Programs, Sustaining Expression of Self-Renewal Genes in Pediatric Brain Cancers Timothy E. Van Meter Asadullah Khan Kevin Fitzmartin Timothy E. Van Meter College of William and Mary Follow this and additional works at: https://scholarworks.wm.edu/aspubs Recommended Citation Van Meter, T. E., Khan, A., Fitzmartin, K., Taylor, M. D., Mack, S., & Cote, J. (2014). Eg-16aberrant Myst4/brpf1 Signaling Misdirects Regional Neurogenesis Programs, Sustaining Expression Of Self-renewal Genes In Pediatric Brain Cancers. Neuro-oncology, 16(Suppl 5), v78. This Article is brought to you for free and open access by the Arts and Sciences at W&M ScholarWorks. It has been accepted for inclusion in Arts & Sciences Articles by an authorized administrator of W&M ScholarWorks. For more information, please contact scholarworks@wm.edu. N E U RO - O N CO LO G YAbstractsEG-16. ABERRANT Myst4/Brpf1 SIGNALING MISDIRECTSREGIONAL NEUROGENESIS PROGRAMS, SUSTAININGEXPRESSION OF SELF-RENEWAL GENES IN PEDIATRIC BRAINCANCERSTimothy E. VanMeter1,2, Asadullah Khan1, Kevin Fitzmartin1, MichaelD. Taylor3, Stephen Mack3, and Jacques Cote4; 1VCU School of Medicine,Richmond,VA,USA; 2College ofWilliamandMary,Williamsburg,VA,USA;3Hospital for Sick Children, Toronto, ON, Canada; 4University of Laval,Quebec, CanadaTheMyst family of acetyltransferase proteins has been shown to play impor-tant role in development and self-renewal, primarily through lysine acetylationon Histones H3 and H4. In neural development, Myst4 (Morf/KAT6B) hasbeen found to be critical for self-renewal and for neuron generation in thedeveloping nervous system and during adult neurogenesis. This chromatinmod-ifier exists in a complex with Myst3 (Moz/KAT6A), the bromodomain factorBrpf1, which acts as a protein scaffold, targeting histone acetyltransferases tochromatin, as well as Inhibitor of Growth 5 (ING5) and Esa1-associated factor6 (EAF6). Our laboratories have found alteration of these elements in pediatricbrain cancers, suggesting a pathological role in abnormal neural progenitorgrowth. Exon-specific microarrays, DNA methylation studies and functionalperturbationwereperformedtostudythe impactontumorbehavior.RNAinter-ference in tumors andneuralprogenitors led to lossofH3K4acetylation in targetgenes and altered expression, including Spondin-1.Conversely, exogenous over-expression of targeting factors, such as Brpf1, enhanced expression of targetgenes, assessed by quantitative PCR analysis. Furthermore, expression ofMyst3/4 and Brpf1 positively correlated with tumor malignancy markers inlarge patient cohorts, including Ki67, PCNA, and MELK, and with decreasedoverall survival. Assessment of direct functional relationships with tumormarkers using ChIP-Seq approaches is currently being pursued to investigatedirect Myst3/4/Brpf1-mediated promoter activity at known and novel targetgenes. These studies aim to elucidate the role of an important epigeneticmecha-nism in neurogenesis, the alteration of which may underlie global chromatinchanges that contribute to tumor growth or initiation. Sustained progenitorgrowth may be suppressed by targeted therapies that disrupt these factors.Neuro-Oncology 16:v75–v78, 2014.doi:10.1093/neuonc/nou254Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2014.Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/16/suppl_5/v78/1053662 by Serials Dept -- College of William and Mary user on 10 December 2018

Aberrant myst4/brpf1 Signaling Misdirects Regional Neurogenesis Programs, Sustaining Expression of Self-Renewal Genes in Pediatric Brain Cancers

https://scholarworks.wm.edu/cgi/viewcontent.cgi?article=1473&context=aspubs

Aberrant myst4/brpf1 Signaling Misdirects Regional Neurogenesis Programs, Sustaining Expression of Self-Renewal Genes in Pediatric Brain Cancers

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