The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Julie C. Baker - One of the best experts on this subject based on the ideXlab platform.
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endogenous retroviruses function as species specific Enhancer Elements in the placenta
Nature Genetics, 2013Co-Authors: Edward B Chuong, Michael J Soares, M Karim A Rumi, Julie C. BakerAbstract:Julie Baker and colleagues report epigenome and transcriptome profiles of rat and mouse trophoblast stem cells and show that endogenous retroviruses serve as a genome-wide source of species-specific Enhancer Elements in the placenta.
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endogenous retroviruses function as species specific Enhancer Elements in the placenta
Nature Genetics, 2013Co-Authors: Edward B Chuong, Michael J Soares, M Karim A Rumi, Julie C. BakerAbstract:Julie Baker and colleagues report epigenome and transcriptome profiles of rat and mouse trophoblast stem cells and show that endogenous retroviruses serve as a genome-wide source of species-specific Enhancer Elements in the placenta. The mammalian placenta is remarkably distinct between species, suggesting a history of rapid evolutionary diversification1. To gain insight into the molecular drivers of placental evolution, we compared biochemically predicted Enhancers in mouse and rat trophoblast stem cells (TSCs) and found that species-specific Enhancers are highly enriched for endogenous retroviruses (ERVs) on a genome-wide level. One of these ERV families, RLTR13D5, contributes hundreds of mouse-specific histone H3 lysine 4 monomethylation (H3K4me1)- and histone H3 lysine 27 acetylation (H3K27ac)-defined Enhancers that functionally bind Cdx2, Eomes and Elf5—core factors that define the TSC regulatory network. Furthermore, we show that RLTR13D5 is capable of driving gene expression in rat placental cells. Analysis in other tissues shows that species-specific ERV Enhancer activity is generally restricted to hypomethylated tissues, suggesting that tissues permissive for ERV activity gain access to an otherwise silenced source of regulatory variation. Overall, our results implicate ERV Enhancer co-option as a mechanism underlying the extensive evolutionary diversification of placental development.
Laurie A Boyer - One of the best experts on this subject based on the ideXlab platform.
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sox2 co occupies distal Enhancer Elements with distinct pou factors in escs and npcs to specify cell state
PLOS Genetics, 2013Co-Authors: Michael A Lodato, Joseph A Wamstad, Albert W Cheng, Kevin K Thai, Ernest Fraenkel, Rudolf Jaenisch, Laurie A BoyerAbstract:SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal Enhancer Elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal Enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal Enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors.
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sox2 co occupies distal Enhancer Elements with distinct pou factors in escs and npcs to specify cell state
PLoS, 2013Co-Authors: Michael A Lodato, Joseph A Wamstad, Albert W Cheng, Kevin K Thai, Ernest Fraenkel, Rudolf Jaenisch, Laurie A BoyerAbstract:SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal Enhancer Elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal Enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal Enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors. Citation: Lodato MA, Ng CW, Wamstad JA, Cheng AW, Thai KK, et al. (2013) SOX2 Co-Occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State. PLoS Genet 9(2): e1003288. doi:10.1371/journal.pgen.1003288 Editor: Gregory S. Barsh, Stanford University School of Medicine, United States of America Received June 22, 2012; Accepted December 15, 2012; Published February 21, 2013 Copyright: 2013 Lodato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by NRSA F32-HL104913 (JAW), NIH R01-GM089903 (EF), NIH 5-R37HD045022 and R01-CA084198 (RJ), and the Richard and Susan Smith Foundation (LAB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: jaenisch@wi.mit.edu (RJ); lboyer@mit.edu (LAB) . These authors contributed equally to this work.
Edward B Chuong - One of the best experts on this subject based on the ideXlab platform.
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endogenous retroviruses function as species specific Enhancer Elements in the placenta
Nature Genetics, 2013Co-Authors: Edward B Chuong, Michael J Soares, M Karim A Rumi, Julie C. BakerAbstract:Julie Baker and colleagues report epigenome and transcriptome profiles of rat and mouse trophoblast stem cells and show that endogenous retroviruses serve as a genome-wide source of species-specific Enhancer Elements in the placenta.
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endogenous retroviruses function as species specific Enhancer Elements in the placenta
Nature Genetics, 2013Co-Authors: Edward B Chuong, Michael J Soares, M Karim A Rumi, Julie C. BakerAbstract:Julie Baker and colleagues report epigenome and transcriptome profiles of rat and mouse trophoblast stem cells and show that endogenous retroviruses serve as a genome-wide source of species-specific Enhancer Elements in the placenta. The mammalian placenta is remarkably distinct between species, suggesting a history of rapid evolutionary diversification1. To gain insight into the molecular drivers of placental evolution, we compared biochemically predicted Enhancers in mouse and rat trophoblast stem cells (TSCs) and found that species-specific Enhancers are highly enriched for endogenous retroviruses (ERVs) on a genome-wide level. One of these ERV families, RLTR13D5, contributes hundreds of mouse-specific histone H3 lysine 4 monomethylation (H3K4me1)- and histone H3 lysine 27 acetylation (H3K27ac)-defined Enhancers that functionally bind Cdx2, Eomes and Elf5—core factors that define the TSC regulatory network. Furthermore, we show that RLTR13D5 is capable of driving gene expression in rat placental cells. Analysis in other tissues shows that species-specific ERV Enhancer activity is generally restricted to hypomethylated tissues, suggesting that tissues permissive for ERV activity gain access to an otherwise silenced source of regulatory variation. Overall, our results implicate ERV Enhancer co-option as a mechanism underlying the extensive evolutionary diversification of placental development.
Stephen J Chanock - One of the best experts on this subject based on the ideXlab platform.
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abstract sy25 01 identification of Enhancer Elements at kidney cancer susceptibility loci using genome wide approaches in which post gwas functional studies implicate the swi snf dpf3 gene for the 14q24 risk locus
Epidemiology, 2019Co-Authors: Leandro M Colli, Mitchell J Machiela, Jiyeon Choi, Timothy G Myers, Lea Jessop J Chanock, Mark P Purdue, Kevin K Brown, Stephen J ChanockAbstract:We investigated the set of common single nucleotide polymorphisms (SNPs) that are highly correlated with 20 renal cancer (RCC) susceptibility regions identified by Genome-wide Association Study (GWAS). Together extensive fine-mapping and in silico functional analyses, based on publicly available resources, we used an integrated approach to pursue regulatory Elements in which one or more variant allele could confer differential functional activity. To this end, we conducted an initial screening Massively Parallel Reporter Assay (MPRA), followed by three additional approaches: 1. Assay for Transposase-Accessible Chromatin (ATAC-seq); 2. RCC eQTL analysis;3. Capture-HiC. We confirmed the effects reported for three regions (8q24, 11q13 and 12p12). We selected 784 SNPs with an r2>0.4 or D’>0.5 and MAF Citation Format: Leandro M. Colli, Lea Jessop J. Chanock, Timothy Myers, Mitchell Machiela, Jiyeon Choi, Mark Purdue, Kevin Brown, Stephen J. Chanock. Identification of Enhancer Elements at kidney cancer susceptibility loci using genome-wide approaches in which post-GWAS functional studies implicate the SWI/SNF DPF3 gene for the 14q24 risk locus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY25-01.
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abstract 1443 identification of Enhancer Elements at kidney cancer susceptibility loci using mpra
Cancer Research, 2017Co-Authors: Leandro M Colli, Lea Jessop, Mitchell J Machiela, Jiyeon Choi, Timothy G Myers, Stephen J ChanockAbstract:GWAS is an important tool for discovering regions in the genome associated with cancer susceptibility. For renal cell carcinoma (RCC), only two loci have had their functional basis explained (11q13 and 12p12). Here, we used a massively parallel reporter assay (MPRA) to investigate Enhancer activity in 20 GWAS regions that had an RCC association p-value of at least 10-7. We selected 784 SNPs with an r2>0.4 or D’>0.5 and MAF Citation Format: Leandro Machado Colli, Lea Jessop, Mitchell Machiela, Jiyeon Choi, Timothy Myers, Stephen Chanock. Identification of Enhancer Elements at kidney cancer susceptibility loci using MPRA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1443. doi:10.1158/1538-7445.AM2017-1443
Michael A Lodato - One of the best experts on this subject based on the ideXlab platform.
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sox2 co occupies distal Enhancer Elements with distinct pou factors in escs and npcs to specify cell state
PLOS Genetics, 2013Co-Authors: Michael A Lodato, Joseph A Wamstad, Albert W Cheng, Kevin K Thai, Ernest Fraenkel, Rudolf Jaenisch, Laurie A BoyerAbstract:SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal Enhancer Elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal Enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal Enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors.
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sox2 co occupies distal Enhancer Elements with distinct pou factors in escs and npcs to specify cell state
PLoS, 2013Co-Authors: Michael A Lodato, Joseph A Wamstad, Albert W Cheng, Kevin K Thai, Ernest Fraenkel, Rudolf Jaenisch, Laurie A BoyerAbstract:SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal Enhancer Elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal Enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal Enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors. Citation: Lodato MA, Ng CW, Wamstad JA, Cheng AW, Thai KK, et al. (2013) SOX2 Co-Occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State. PLoS Genet 9(2): e1003288. doi:10.1371/journal.pgen.1003288 Editor: Gregory S. Barsh, Stanford University School of Medicine, United States of America Received June 22, 2012; Accepted December 15, 2012; Published February 21, 2013 Copyright: 2013 Lodato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by NRSA F32-HL104913 (JAW), NIH R01-GM089903 (EF), NIH 5-R37HD045022 and R01-CA084198 (RJ), and the Richard and Susan Smith Foundation (LAB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: jaenisch@wi.mit.edu (RJ); lboyer@mit.edu (LAB) . These authors contributed equally to this work.
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histone h3k27ac separates active from poised Enhancers and predicts developmental state
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Menno P Creyghton, Michael A Lodato, Albert W Cheng, Grant G Welstead, Tristan Kooistra, Bryce W Carey, Eveline J Steine, Jacob H Hanna, Garrett M Frampton, Phillip A SharpAbstract:Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at Enhancers contribute to the specific gene expression programs that determine cell state and the potential for differentiation into new cell types. Although Enhancer Elements are known to be associated with certain histone modifications and transcription factors, the relationship of these modifications to gene expression and developmental state has not been clearly defined. Here we interrogate the epigenetic landscape of Enhancer Elements in embryonic stem cells and several adult tissues in the mouse. We find that histone H3K27ac distinguishes active Enhancers from inactive/poised Enhancer Elements containing H3K4me1 alone. This indicates that the amount of actively used Enhancers is lower than previously anticipated. Furthermore, poised Enhancer networks provide clues to unrealized developmental programs. Finally, we show that Enhancers are reset during nuclear reprogramming.