Publications by authors named "Ilana Livyatan"

9 Publications

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Characterization of the human tumor microbiome reveals tumor-type specific intra-cellular bacteria.

Oncoimmunology 2020 07 29;9(1):1800957. Epub 2020 Jul 29.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Many characteristics of cancer such as proliferation, survival, progression, immunogenicity, sensitivity, and resistance to therapy are not just endogenously driven by the tumor cells themselves, but are greatly affected by their interaction with the components of their microenvironment. In our recent report, we comprehensively characterized the bacterial content of solid tumors, which is strongly related to tumor type and subtype, largely presenting as metabolically-active and intra-cellular. Our integration with clinical patient data indicates potential avenues of cross-talk between the tumors and their bacterial counterparts paving the way for a deeper understanding of the physiological/biological context of the tumor and how to harness bacteria in therapy settings.
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http://dx.doi.org/10.1080/2162402X.2020.1800957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466861PMC
July 2020

The human tumor microbiome is composed of tumor type-specific intracellular bacteria.

Science 2020 05;368(6494):973-980

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients' smoking status, and the response to immunotherapy.
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http://dx.doi.org/10.1126/science.aay9189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757858PMC
May 2020

Systematic identification of gene family regulators in mouse and human embryonic stem cells.

Nucleic Acids Res 2016 05 15;44(9):4080-9. Epub 2016 Apr 15.

Department of Genetics, The Alexander Silberman Institute of Life Sciences, Jerusalem 91904, Israel The Edmond and Lily Center for Brain Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel

Pluripotent self-renewing embryonic stem cells (ESCs) have been the focus of a growing number of high-throughput experiments, revealing the genome-wide locations of hundreds of transcription factors and histone modifications. While most of these datasets were used in a specific context, all datasets combined offer a comprehensive view of chromatin characteristics and regulatory elements that govern cell states. Here, using hundreds of datasets in ESCs, we generated colocalization maps of chromatin proteins and modifications, and built a discovery pipeline for regulatory proteins of gene families. By comparing genome-wide binding data with over-expression and knockdown analysis of hundreds of genes, we discovered that the pluripotency-related factor NR5A2 separates mitochondrial from cytosolic ribosomal genes, regulating their expression. We further show that genes with a common chromatin profile are enriched for distinct Gene Ontology (GO) categories. Our approach can be generalized to reveal common regulators of any gene group; discover novel gene families, and identify common genomic elements based on shared chromatin features.
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http://dx.doi.org/10.1093/nar/gkw259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872113PMC
May 2016

BindDB: An Integrated Database and Webtool Platform for "Reverse-ChIP" Epigenomic Analysis.

Cell Stem Cell 2015 Dec;17(6):647-648

Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel; The Edmond and Lily Center for Brain Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel. Electronic address:

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http://dx.doi.org/10.1016/j.stem.2015.11.015DOI Listing
December 2015

Differential association of chromatin proteins identifies BAF60a/SMARCD1 as a regulator of embryonic stem cell differentiation.

Cell Rep 2015 Mar 26;10(12):2019-31. Epub 2015 Mar 26.

Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Electronic address:

Embryonic stem cells (ESCs) possess a distinct chromatin conformation maintained by specialized chromatin proteins. To identify chromatin regulators in ESCs, we developed a simple biochemical assay named D-CAP (differential chromatin-associated proteins), using brief micrococcal nuclease digestion of chromatin, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Using D-CAP, we identified several differentially chromatin-associated proteins between undifferentiated and differentiated ESCs, including the chromatin remodeling protein SMARCD1. SMARCD1 depletion in ESCs led to altered chromatin and enhanced endodermal differentiation. Gene expression and chromatin immunoprecipitation sequencing (ChIP-seq) analyses suggested that SMARCD1 is both an activator and a repressor and is enriched at developmental regulators and that its chromatin binding coincides with H3K27me3. SMARCD1 knockdown caused H3K27me3 redistribution and increased H3K4me3 around the transcription start site (TSS). One of the identified SMARCD1 targets was Klf4. In SMARCD1-knockdown clones, KLF4, as well as H3K4me3 at the Klf4 locus, remained high and H3K27me3 was abolished. These results propose a role for SMARCD1 in restricting pluripotency and activating lineage pathways by regulating H3K27 methylation.
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http://dx.doi.org/10.1016/j.celrep.2015.02.064DOI Listing
March 2015

SON sheds light on RNA splicing and pluripotency.

Nat Cell Biol 2013 Oct;15(10):1139-40

Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra (Givat Ram) Campus, Jerusalem, 91904, Israel.

The role of RNA splicing in the regulation of stem cell properties has remained largely unexplored. The splicing-associated protein SON is now shown to be necessary for embryonic stem cell maintenance, by influencing the splicing of pluripotency regulators.
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http://dx.doi.org/10.1038/ncb2851DOI Listing
October 2013

The HDAC interaction network.

Mol Syst Biol 2013 ;9:671

Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem, Israel.

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http://dx.doi.org/10.1038/msb.2013.33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964317PMC
September 2013

Non-polyadenylated transcription in embryonic stem cells reveals novel non-coding RNA related to pluripotency and differentiation.

Nucleic Acids Res 2013 Jul 29;41(12):6300-15. Epub 2013 Apr 29.

Hebrew University of Jerusalem, Jerusalem 91904, Israel.

The transcriptional landscape in embryonic stem cells (ESCs) and during ESC differentiation has received considerable attention, albeit mostly confined to the polyadenylated fraction of RNA, whereas the non-polyadenylated (NPA) fraction remained largely unexplored. Notwithstanding, the NPA RNA super-family has every potential to participate in the regulation of pluripotency and stem cell fate. We conducted a comprehensive analysis of NPA RNA in ESCs using a combination of whole-genome tiling arrays and deep sequencing technologies. In addition to identifying previously characterized and new non-coding RNA members, we describe a group of novel conserved RNAs (snacRNAs: small NPA conserved), some of which are differentially expressed between ESC and neuronal progenitor cells, providing the first evidence of a novel group of potentially functional NPA RNA involved in the regulation of pluripotency and stem cell fate. We further show that minor spliceosomal small nuclear RNAs, which are NPA, are almost completely absent in ESCs and are upregulated in differentiation. Finally, we show differential processing of the minor intron of the polycomb group gene Eed. Our data suggest that NPA RNA, both known and novel, play important roles in ESCs.
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http://dx.doi.org/10.1093/nar/gkt316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695530PMC
July 2013

Multilayered chromatin analysis reveals E2f, Smad and Zfx as transcriptional regulators of histones.

Nat Struct Mol Biol 2013 Jan 9;20(1):119-26. Epub 2012 Dec 9.

Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

Histones, the building blocks of eukaryotic chromatin, are essential for genome packaging, function and regulation. However, little is known about their transcriptional regulation. Here we conducted a comprehensive computational analysis, based on chromatin immunoprecipitation-sequencing and -microarray analysis (ChIP-seq and ChIP-chip) data of over 50 transcription factors and histone modifications in mouse embryonic stem cells. Enrichment scores supported by gene expression data from gene knockout studies identified E2f1 and E2f4 as master regulators of histone genes, CTCF and Zfx as repressors of core and linker histones, respectively, and Smad1, Smad2, YY1 and Ep300 as restricted or cell type-specific regulators. We propose that histone gene regulation is substantially more complex than previously thought, and that a combination of factors orchestrate histone gene regulation, from strict synchronization with S phase to targeted regulation of specific histone subtypes.
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http://dx.doi.org/10.1038/nsmb.2448DOI Listing
January 2013