Abstract

The histone H3 mutations found recently found in cancers have dramatic downstream effects on the landscape of the epigenome ? chromatin state and DNA methylation ? with eventual secondary outcomes manifested in gene expression and cellular phenotypes. Modern functional genomics approaches provide invaluable tools to study the effects of this epigenome-mediated cascade. In this Core activity, we will establish a set of genomics tools and computation methods to elucidate the mechanisms through which H3 variants impact the epigenome, transcriptome, and finally the cell during neoplastic transformation.

Public Health Relevance

Cancer progression is associated with massive global aberrations of genome and epigenome organization. Modern genomics technologies have provided invaluable new insights into molecular mechanisms of cancers, including the discovery by our team members of the histone mutations that are the subject of this proposal. The establishment of this Core will provide team members with state of the art genomic and computational tools to unravel the mechanisms of action of histone mutations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA196539-03
Application #
9342737
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Simithy, Johayra; Sidoli, Simone; Garcia, Benjamin A (2018) Integrating Proteomics and Targeted Metabolomics to Understand Global Changes in Histone Modifications. Proteomics 18:e1700309
Di Marcantonio, Daniela; Martinez, Esteban; Sidoli, Simone et al. (2018) Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia. Clin Cancer Res 24:608-618
Valera, Elvis Terci; McConechy, Melissa K; Gayden, Tenzin et al. (2018) Methylome analysis and whole-exome sequencing reveal that brain tumors associated with encephalocraniocutaneous lipomatosis are midline pilocytic astrocytomas. Acta Neuropathol 136:657-660
Wojcik, Felix; Dann, Geoffrey P; Beh, Leslie Y et al. (2018) Functional crosstalk between histone H2B ubiquitylation and H2A modifications and variants. Nat Commun 9:1394
Lee, Chul-Hwan; Yu, Jia-Ray; Kumar, Sunil et al. (2018) Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin. Mol Cell 70:422-434.e6
Guo, Qi; Sidoli, Simone; Garcia, Benjamin A et al. (2018) Assessment of Quantification Precision of Histone Post-Translational Modifications by Using an Ion Trap and down To 50?000 Cells as Starting Material. J Proteome Res 17:234-242
Weiner, Amber K; Sidoli, Simone; Diskin, Sharon J et al. (2018) Graphical Interpretation and Analysis of Proteins and their Ontologies (GiaPronto): A One-Click Graph Visualization Software for Proteomics Data Sets. Mol Cell Proteomics 17:1426-1431
Gomes, Carolina Cavalieri; Gayden, Tenzin; Bajic, Andrea et al. (2018) TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw. Nat Commun 9:4572
Shastrula, Prashanth Krishna; Lund, Peder J; Garcia, Benjamin A et al. (2018) Rpp29 regulates histone H3.3 chromatin assembly through transcriptional mechanisms. J Biol Chem 293:12360-12377
Bharathy, Narendra; Berlow, Noah E; Wang, Eric et al. (2018) The HDAC3-SMARCA4-miR-27a axis promotes expression of the PAX3:FOXO1 fusion oncogene in rhabdomyosarcoma. Sci Signal 11:

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