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Researchers
  • Prof.  Ben Berman
Dr. Ben Berman
 
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The Methyl Grammar lab at Hebrew University

This is the website of the Ben Berman lab at The Hebrew University of Jerusalem. Our goal is to understand the genomic patterns of DNA methylation and other epigenomic markers that underlie gene regulation in human development and disease. Informative patterns and signatures can be discovered across a wide range of genomic scales, and our lab is dedicated to the development of compuatational tools and software packages to address this challenge and identify clinically-relevant epigenomic biomarkers. See our Research page for more details.
Shown to the left are examples of multi-scale mapping of DNA methylation features: (1) Allele-specific methylation across a 70 base pair (bp) region encompassing the H19 imprinting control element, (2) phased methylation pattern representing regularly-spaced nucleosomes in 2,000 bp regions centered on a transcription factor binding site CTCF (middle), and (3) decreased methylation within long domains within a 30 million bp chromosome arm (bottom).
If you are interested in joining us as an MS, PhD student or postdoctoral researcher, please see our Job openings page. We are always looking for talented new scientists
Research

Reconstructing altered transcription factor networks from chromatin changes at cis-regulatory elements

Our lab is interested in the reconstruction of cancer gene regulatory networks from DNA methylation and other chromatin changes that occur at transcription factor binding sites (TFBSs). For instance, we collaborated with Peter Jones’ lab to develop the multi-omic NOMe-seq technique for determining the differing roles of DNA methylation and chromatin accessibility at TFBSs (Kelly et al., Genome Res. 2010), and developed a computational approach Bis-SNP to deconvolute methylation and SNP information from bisulfite sequencing to identify allele-specific TFBSs (Liu et al., Genome Biol. 2012). We developed a Bioconductor R package, ELMER, that integrates DNA methylation information at TFBSs with TF expression levels to reconstruct gene regulatory networks (Yao et al., Genome Biol. 2015; Silva et al., Bioinformatics 2018).

 

 

 

 

Heterochromatin-associated methylation loss in aging and cancer

We collaborated with Peter Jones’ lab to use DNA Methyltransferase (DNMT) knockouts in colon cancer cells to study the effects of global methylation loss, showing dramatic changes in the epigenomic architecture of a large number of non-coding gene regulatory regions and expression of nearby genes (Lay et al., Genome Res. 2015). Turning to in vivo data, we recently compiled methylation data from ~15,000 publicly available tissue samples, and developed a new computational model to discover that Heterochromatin-Associated Methylation Loss begins early in life and behaves as a mitotic clock (Zhou et al., Nat. Genetics 2018).

 

 

 

 


Understanding cancer evolution through epigenetic intra-tumour heterogeneity

We collaborated with Phil Koeffler’s lab to investigate the genetic and epigenetic heterogeneity of individual cancer cases by sequencing multiple geographic sites from the same tumour. In oesophageal cancer, we found that DNA methylation changes followed a similar evolutionary path as the genome (Hao et al., Nat. Genetics 2016), while we found significant divergence in liver cancer (Lin et al., Cancer Res.2017).

 

 

 

 

 

 

Lab Members
Ben Berman 
Ben Berman, PhD
Principal Investigator
Publications
10 core papers selected from 57 peer-reviewed Berman lab publications. A complete list of publications is available at my Google Scholar page or my PubMed page.
Silva, Tiago C et al. "ELMER v.2: an R/Bioconductor package to reconstruct gene regulatory networks from DNA methylation and transcriptome profiles". Bioinformatics, 2018 doi:10.1093/bioinformatics/bty902
Zhou, Wanding et al. "DNA methylation loss in late-replicating domains is linked to mitotic cell division". Nature Genetics, 2018 doi:10.1038/s41588-018-0073-4
Lin, De-Chen et al. "Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas". Gut, 2018 doi:10.1136/gutjnl-2017-314607
de Couto, Geoffrey et al. "Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning". Circulation, 2017 doi:10.1161/circulationaha.116.024590
Hao, Jia-Jie et al. "Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma". Nature Genetics, 2016 doi:10.1038/ng.3683
Yao, Lijing et al. "Inferring regulatory element landscapes and transcription factor networks from cancer methylomes". Genome Biology, 2015 doi:10.1186/s13059-015-0668-3
Lay, Fides D. et al. "The role of DNA methylation in directing the functional organization of the cancer epigenome". Genome Research, 2015 doi:10.1101/gr.183368.114
Kelly, T. K. et al. "Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules". Genome Research, 2012 doi:10.1101/gr.143008.112
Liu, Yaping et al. "Bis-SNP: Combined DNA methylation and SNP calling for Bisulfite-seq data". Genome Biology, 2012 doi:10.1186/gb-2012-13-7-r61
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