Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities
Sven Heinz,Christopher Benner,Nathanael J. Spann,Eric Bertolino,Yin C. Lin,Peter Laslo,Jason X. Cheng,Cornelis Murre,Harinder Singh,Harinder Singh,Christopher K. Glass +10 more
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TLDR
It is demonstrated in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B cell lineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions.About:
This article is published in Molecular Cell.The article was published on 2010-05-28 and is currently open access. It has received 9620 citations till now. The article focuses on the topics: Pioneer factor & General transcription factor.read more
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TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity
TL;DR: Data indicate that TP53, along with TP63, may act as pioneer factors to specify epithelial enhancers and suggest that rather than following a global cell-type invariant stress response program, TP53 may tune its response based on the lineage-specific epigenomic landscape.
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Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells
Mara Compagno,Qi Wang,Chiara Pighi,Taek-Chin Cheong,Fei-Long Meng,Teresa Poggio,Leng-Siew Yeap,Elif Karaca,Rafael B Blasco,Fernanda Langellotto,Chiara Ambrogio,Claudia Voena,Claudia Voena,Adrian Wiestner,Siddha Kasar,Jennifer R. Brown,Jing Sun,Catherine J. Wu,Monica Gostissa,Frederick W. Alt,Roberto Chiarle,Roberto Chiarle +21 more
TL;DR: It is shown that PI3Kδ or Bruton’s tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism.
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Dnmt3a restrains mast cell inflammatory responses
Cristina Leoni,Cristina Leoni,Sara Montagner,Andrea Rinaldi,Francesco Bertoni,Sara Polletti,Chiara Balestrieri,Silvia Monticelli +7 more
TL;DR: Using mast cells lacking Dnmt3a, it is found that this enzyme is involved in restraining mast cell responses to acute and chronic stimuli, both in vitro and in vivo.
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An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression.
Yufeng Qin,John Roberts,Sara A. Grimm,Fred B. Lih,Leesa J. Deterding,Ruifang Li,Kaliopi Chrysovergis,Paul A. Wade +7 more
TL;DR: These findings suggest that the gut microbiome, under specific dietary exposures, stimulates a reprogramming of the enhancer landscape in the colon, with downstream effects on transcription factors, which may be associated with those seen during colon cancer development.
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Tumor cell-intrinsic EPHA2 suppresses anti-tumor immunity by regulating PTGS2 (COX-2)
Nune Markosyan,Jinyang Li,Yu H. Sun,Lee P. Richman,Jeffrey H. Lin,Fangxue Yan,Liz Quinones,Yogev Sela,Taiji Yamazoe,Naomi Gordon,John W. Tobias,Katelyn T. Byrne,Andrew J. Rech,Garret A. FitzGerald,Ben Z. Stanger,Robert H. Vonderheide +15 more
TL;DR: The findings warrant clinical trials testing the effectiveness of therapies combining EPHA2-TGFβ-PTGS2 pathway inhibitors with anti-tumor immunotherapy, and may change the treatment of notoriously therapy-resistant pancreatic adenocarcinoma.
References
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TL;DR: The introduction of a mutation in RAG-1 into the germline of mice via gene targeting in embryonic stem cells is described and it is shown that this mutation either activates or catalyzes the V(D)J recombination reaction of immunoglobulin and T cell receptor genes.
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TL;DR: This study uses chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing to map the locations of TF-binding sites and identifies important features of the transcriptional regulatory networks that define ES-cell identity.
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Genome-scale DNA methylation maps of pluripotent and differentiated cells
Alexander Meissner,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Hongcang Gu,Marius Wernig,Jacob H. Hanna,Andrey Sivachenko,Xiaolan Zhang,Bradley E. Bernstein,Bradley E. Bernstein,Chad Nusbaum,David B. Jaffe,Andreas Gnirke,Rudolf Jaenisch,Eric S. Lander +14 more
TL;DR: Low-throughput reduced representation bisulphite sequencing is established as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.