Benjamin P. Berman

Benjamin Berman

Positions

  • Assistant Professor, Division of Bioinformatics, Department of Preventive Medicine, USC
  • Member, USC Epigenome Center, USC
  • Member, Norris Comprehensive Cancer Center, USC

 

Contact information
Prof. Benjamin Berman
University of Southern California
1450 Biggy Street #G511
Los Angeles, CA 90089-9601
phone: (323) 442-7820
fax: (323) 442-7880
email: bberman atsymbol usc dot edu

 

Research interests

1. Whole-genome epigenomic analysis of cancer. Research during the past several years has uncovered an array of chromatin changes that control gene regulation during development, cellular differentiation, and disease. Whole-genome chromatin maps are being generated using sequence-based technologies to identify protein binding sites, post-translational modifications to core histone proteins, and methylation groups attached to genomic cytosines. In parallel, large-scale cancer mutation sequencing projects have identified chromatin modifiers as one of the most frequently mutated gene classes. We are developing lab and computational tools to integrate epigenomic maps of primary tumors and cancer cell models to understand the connections between chromatin modifier mutations, epigenomic changes, and gene regulation. We have developed a software pipeline, Bis-SNP, to extract methylation and single-nucleotide polymorphism (SNP) information from whole-genome DNA methylation experiments, and are using this pipeline to investigate patient tumor samples from The Cancer Genome Atlas (TCGA) consortium. We are currently focused on the deconvolution of epigenomic patterns that typically occur in these samples due to the heterogeneous mixture of cancer and other cells that make up the tumor.

2. Control of gene regulation by non-coding regulatory elements. Complex gene regulation in humans relies on hundreds of thousands of short non-coding regulatory sequences that appear throughout the genome as cataloged by individual labs and encyclopedic projects such as ENCODE. Activation of these elements often coincides with increased chromatin accessibility and stereotyped changes in histone modifications and DNA methylation. We have worked with USC collaborators to develop a whole-genome sequencing method called Nucleosome Occupancy and DNA Methylation sequencing (NOMe-seq) to measure chromatin accessibility and DNA methylation simultaneously within individual cells, providing a combinatorial epigenomic profile. We are developing software tools for analysis of NOMe-seq data, and applying these tools to identify novel non-coding regulatory elements in cancer cells. These combined data can be useful for understanding the involvement of specific upstream pathways in activating transcription factors or other chromatin modifying proteins to control regulatory elements and gene expression.

3. Role of nuclear organization alterations in cancer. An emerging picture suggests that key nuclear processes of transcription, DNA replication, and repair are jointly coordinated via the spatial organization of chromosomes within the cell nucleus. Our work and the recent work of others have shown that in cancer, these higher-order nuclear changes are reflected as changes to the long-range domain structure of epigenetic signals in the genome. We hypothesize that chromosomal aberrations that arise in cancer can lead to abnormal nuclear organization and give rise to tumor-promoting transcriptional changes (either by gene activation or gene silencing). We are using whole-genome cancer sequencing data to investigate transcriptional and epigenomic changes that occur adjacent to common chromosomal aberration breakpoints.

 

Project-specific websites

 

Selected Publications

  • Adams MD, et al., including Berman BP, and others. (2000). “The genome sequence of Drosophila melanogaster.” Science 287(5461): 2185-95. PMID: 10731132

  • Hoskins RA, Nelson CR, Berman BP, Laverty TR, George RA, Ciesiolka L, Naeemuddin M, Arenson AD, Durbin J, David RG, Tabor PE, Bailey MR, DeShazo DR, Catanese J, Mammoser A, Osoegawa K, de Jong PJ, Celniker SE, Gibbs RA, Rubin GM, Scherer SE (2000). “A BAC-based physical map of the major autosomes of Drosophila melanogaster.” Science 287(5461):2271-4. PMID: 10731150

  • Berman BP, Nibu Y, Pfeiffer BD, Tomancak P, Celniker SE, Levine M, Rubin GM, Eisen MB. (2002). “Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome.” Proc Natl Acad Sci U S A 99(2): 757-62. PMID: 11805330

  • Berman BP*, Pfeiffer BD, Laverty TR, Salzberg SL, Rubin GM, Eisen MB, Celniker SE. (2004). “Computational identification of developmental enhancers: conservation and function of transcription factor binding-site clusters in Drosophila melanogaster and Drosophila pseudoobscura.” Genome Biology 5(9):R61. PMID: 15345045

  • Tomancak P, Berman BP*, Beaton A, Weiszmann R, Kwan E, Hartenstein V, Celniker SE, Rubin GM. (2007). “Global analysis of patterns of gene expression during Drosophila embryogenesis.” Genome Biology 8(7):R145. PMID: 17645804

  • Jia L, Berman BP*, Jariwala U, Yan X, Cogan JP, Walters A, Chen T, Buchanan G, Frenkel B, Coetzee GA. (2008). “Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity”. PLoS ONE 2008 vol. 3 (11) pp. e3645. PMID: 18997859

  • Jia L, Landan G, Pomerantz M, Jaschek R, Herman P, Reich D, Yan C, Khalid O, Kantoff P, Oh W, Manak JR, Berman BP, Henderson BE, Frenkel B, Haiman CA, Freedman M, Tanay A, Coetzee GA. (2009) “Functional enhancers at the gene-poor 8q24 cancer-linked locus”. PLoS Genetics 5(8):e1000597. PMID: 19680443

  • Berman BP, Weisenberger DJ, Laird PW. (2009) “Locking in on the human methylome”. Nature Biotechnology 27 (4) pp. 341-2. PMID: 19352369

  • Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K (2010). “Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma”. Cancer Cell. 17 (5) pp. 510-22. PMID: 20399149

  • Berman BP, Frenkel B, Coetzee GA, Jia L (2010). “Androgen receptor responsive enhancers are flanked by consistently-positioned H3-acetylated nucleosomes”. Cell Cycle 9(11):2249-50. PMID: 20495358

  • Kelly TK, Miranda TB, Liang G, Berman BP, Lin JC, Tana A, Jones PA (2010). “H2A.Z Maintenance During Mitosis Reveals Nucleosome Shifting on Mitotically Silenced Genes”. Molecular Cell 39 (6) pp.901-11. PMID: 20864037

  • Berman BP, Weisenberger DJ, Aman JF, Hinoue T, Ramjan Z, Liu Y, Noushmehr H, Lange CPE, van Dijk CM, Tollenaar R, Van Den Berg D, Laird PW (2011) “Regions of Focal DNA Hypermethylation and Long-Range Hypomethylation in Colorectal Cancer Coincide with Nuclear Lamina-Associated Domains.” Nature Genetics. 2011 Nov 27;44(1):40-6. PMID: 22120008

  • Liu Y, Siegmund KD, Laird PW, Berman BP (2012) “Bis-SNP: Combined cytosine methylation and SNP calling for bisulfite sequence data.” Genome Biology, 2012 Jul 11;13(7):R61. PMID: 22784381

  • The Cancer Genome Atlas Research Network, including Laird PW, Berman BP, and others (2012): “Comprehensive Molecular Characterization of Human Colon and Rectal Cancer.” Nature, 2012 Jul 18;487(7407):330-7. PMID: 22810696

  • Kelly TK, Liu Y, Lay FD, Liang G, Berman BP*, Jones PA*: “Genome-wide Mapping of Nucleosome Positioning and DNA Methylation Within Individual DNA Molecules.” Genome Research, 2012 Sep 7. PMID: 22960375

* Equal contribution