Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities

doi:10.1016/J.MOLCEL.2010.05.004

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Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities

Journal Article•DOI•

Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities

Sven Heinz¹, Christopher Benner¹, Nathanael J. Spann¹, Eric Bertolino², Yin C. Lin¹, Peter Laslo³, Jason X. Cheng², Cornelis Murre¹, Harinder Singh⁴, Harinder Singh², Christopher K. Glass¹ - Show less +7 more•Institutions (4)

University of California, San Diego¹, University of Chicago², University of Leeds³, Genentech⁴

28 May 2010-Molecular Cell (NIH Public Access)-Vol. 38, Iss: 4, pp 576-589

TL;DR: 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.

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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.

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Journal Article•DOI•

Comprehensive Integration of Single-Cell Data.

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Tim Stuart, Andrew Butler¹, Paul J. Hoffman, Christoph Hafemeister, Efthymia Papalexi¹, William M. Mauck¹, Yuhan Hao¹, Marlon Stoeckius², Peter Smibert², Rahul Satija¹ - Show less +6 more•Institutions (2)

New York University¹, Harvard University²

13 Jun 2019-Cell

TL;DR: A strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities.

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7,892 citations

Cites background or methods from "Simple Combinations of Lineage-Dete..."

...We searched for overrepresented DNA sequence motifs in accessible regions using the Homer package [Heinz et al., 2010], using the findMotifsGenome....
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...10 Heinz et al., 2010 http://homer.ucsd.edu/homer/ R R Core https://www.r-project.org/ Python Python Software Foundation https://www.python.org/...
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...We searched for overrepresented DNA sequence motifs in accessible regions using the Homer package [Heinz et al., 2010], using the findMotifsGenome.pl program with default parameters, and the mm9 genome....
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Journal Article•DOI•

deepTools2: a next generation web server for deep-sequencing data analysis

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Fidel Ramírez¹, Devon Ryan¹, Björn Grüning², Vivek Bhardwaj¹, Fabian Kilpert¹, Andreas S. Richter¹, Steffen Heyne¹, Friederike Dündar³, Thomas Manke¹ - Show less +5 more•Institutions (3)

Max Planck Society¹, University of Freiburg², Cornell University³

08 Jul 2016-Nucleic Acids Research

TL;DR: An update to the Galaxy-based web server deepTools, which allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches, is presented.

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Abstract: We present an update to our Galaxy-based web server for processing and visualizing deeply sequenced data. Its core tool set, deepTools, allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches. Since we first described our deepTools Galaxy server in 2014, we have implemented new solutions for many requests from the community and our users. Here, we introduce significant enhancements and new tools to further improve data visualization and interpretation. deepTools continue to be open to all users and freely available as a web service at deeptools.ie-freiburg.mpg.de The new deepTools2 suite can be easily deployed within any Galaxy framework via the toolshed repository, and we also provide source code for command line usage under Linux and Mac OS X. A public and documented API for access to deepTools functionality is also available.

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4,359 citations

Additional excerpts

...The rapidly increasing diversity of experimental assays using high-throughput sequencing has led to a concomitant increase in the number of analysis packages that allow for insightful visualization and downstream analyses (e.g. ChAsE (1), the ChIP-seq web server (http://ccg. vital-it.ch/chipseq), Genomation (2), Homer (3), ngs.plot (4))....
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...ch/chipseq), Genomation (2), Homer (3), ngs....
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Journal Article•DOI•

Histone H3K27ac separates active from poised enhancers and predicts developmental state

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Menno P. Creyghton¹, Albert W. Cheng, G. Grant Welstead, Tristan Kooistra, Bryce W. Carey, Eveline J. Steine, Jacob H. Hanna, Michael A. Lodato, Garrett M. Frampton, Phillip A. Sharp, Laurie A. Boyer, Richard A. Young, Rudolf Jaenisch - Show less +9 more•Institutions (1)

Massachusetts Institute of Technology¹

14 Dec 2010-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: The epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse is interrogated and it is found that histone H3K27ac distinguishes active enhancers from inactive/poised enhancers and poised enhancer networks provide clues to unrealized developmental programs.

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Abstract: 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.

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3,541 citations

Cites methods from "Simple Combinations of Lineage-Dete..."

...Examination of ChIP-Seq data (7, 24) confirmed that both Foxa2 and PU....
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Journal Article•DOI•

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes

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Warren A. Whyte¹, David A. Orlando¹, Denes Hnisz¹, Brian J. Abraham¹, Charles Y. Lin¹, Charles Y. Lin², Michael H. Kagey¹, Peter B. Rahl¹, Tong Ihn Lee¹, Richard A. Young¹ - Show less +6 more•Institutions (2)

Massachusetts Institute of Technology¹, Harvard University²

11 Apr 2013-Cell

TL;DR: In this article, the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state, called super-enhancers, which consist of clusters of enhancers that are densely occupied by the master regulators and Mediator.

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2,978 citations

Journal Article•DOI•

Regulatory T Cells: Mechanisms of Differentiation and Function

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Steven Z. Josefowicz¹, Li-Fan Lu², Alexander Y. Rudensky³•Institutions (3)

Howard Hughes Medical Institute¹, Rockefeller University², University of California, San Diego³

26 Mar 2012-Annual Review of Immunology

TL;DR: Cellular and molecular mechanisms in the differentiation and function of regulatory T cells and their role in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation are discussed.

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Abstract: The immune system has evolved to mount an effective defense against pathogens and to minimize deleterious immune-mediated inflammation caused by commensal microorganisms, immune responses against self and environmental antigens, and metabolic inflammatory disorders. Regulatory T (Treg) cell–mediated suppression serves as a vital mechanism of negative regulation of immune-mediated inflammation and features prominently in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation. The discovery that Foxp3 is the transcription factor that specifies the Treg cell lineage facilitated recent progress in understanding the biology of regulatory T cells. In this review, we discuss cellular and molecular mechanisms in the differentiation and function of these cells.

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2,356 citations

Cites background from "Simple Combinations of Lineage-Dete..."

...1 is required for the maintenance of cell type– specific regulatory chromatin characteristics following macrophage and B cell differentiation (153, 154)....
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References

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Open Access

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Journal Article•DOI•

Histone modifications at human enhancers reflect global cell-type-specific gene expression

[...]

Nathaniel D. Heintzman¹, Gary C. Hon¹, R. David Hawkins¹, Pouya Kheradpour², Alexander Stark², Alexander Stark³, Lindsey F. Harp¹, Zhen Ye¹, Leonard K. Lee¹, Rhona K. Stuart¹, Christina W. Ching¹, Keith A. Ching¹, Jessica Antosiewicz-Bourget⁴, Hui Liu⁵, Xinmin Zhang⁵, Roland D. Green⁵, Victor V. Lobanenkov⁶, Ron Stewart⁴, James A. Thomson⁷, James A. Thomson⁴, Gregory E. Crawford⁸, Manolis Kellis³, Manolis Kellis², Bing Ren¹ - Show less +20 more•Institutions (8)

University of California, San Diego¹, Massachusetts Institute of Technology², Broad Institute³, Morgridge Institute for Research⁴, Hoffmann-La Roche⁵, National Institutes of Health⁶, University of Wisconsin-Madison⁷, Duke University⁸

07 May 2009-Nature

TL;DR: The results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.

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Abstract: The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.

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2,320 citations

"Simple Combinations of Lineage-Dete..." refers background in this paper

...1 Induces Sequential Nucleosome Remodeling and Histone H3K4 Monomethylation Recent studies have demonstrated that lineage-determining transcription factors preferentially associate with genomic regions marked by cell type-specific patterns of histone modifications, such as monomethylation of H3K4 (H3K4me1), that are suggested to signify accessible chromatin and/or enhancer-like elements (Heintzman et al., 2009)....
[...]
...…PU.1 binding leads to deposition of the H3K4me1 mark at promoter-distal sites that are correlated with cell type-specific patterns of gene expression (Heintzman et al., 2009) provides the initial evidence that PU.1 contributes to the ‘‘writing’’ of this epigenetic signature on a genome-wide scale....
[...]
...1 binding leads to deposition of the H3K4me1 mark at promoter-distal sites that are correlated with cell type-specific patterns of gene expression (Heintzman et al., 2009) provides the initial evidence that PU....
[...]
...…involved (Boyes and Felsenfeld, 1996; Miller and Widom, 2003), and binding to chromatin marked in a cell type-specific manner by lysine 4-methylated histone H3 (H3K4me1/2) (Lupien et al., 2008), a sign of open chromatin that is correlated withactivity of nearby genes (Heintzman et al., 2009)....
[...]
...…transcription factors preferentially associate with genomic regions marked by cell type-specific patterns of histone modifications, such as monomethylation of H3K4 (H3K4me1), that are suggested to signify accessible chromatin and/or enhancer-like elements (Heintzman et al., 2009)....
[...]

Journal Article•

Histone Modifications at Human Enhancers Reflect Global Cell-Type-Specific Gene Expression

[...]

Nathaniel D. Heintzman, Gary C. Hon, R. David Hawkins, Pouya Kheradpour, Alexander Stark, Lindsey F. Harp, Zhen Ye, Leonard K. Lee, Rhona K. Stuart, Christina W. Ching, Keith A. Ching, Jessica Antosiewicz-Bourget, Hui Liu, Xinmin Zhang, Roland D. Green, Victor V. Lobanenkov, Ron Stewart, James A. Thomson, Gregory E. Crawford, Manolis Kellis, Bing Ren - Show less +17 more

01 Mar 2009-PubMed Central

TL;DR: In this article, a chromatin-immunoprecipitation-based microarray method (ChIP-chip) was used to locate promoters, enhancers and insulators in the human genome and investigate their roles in cell-type specific gene expression.

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2,006 citations

Journal Article•DOI•

Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals

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Xiaohui Xie¹, Jun Lu¹, Edward J. Kulbokas¹, Todd R. Golub¹, Vamsi K. Mootha¹, Kerstin Lindblad-Toh¹, Eric S. Lander², Eric S. Lander¹, Manolis Kellis², Manolis Kellis¹ - Show less +6 more•Institutions (2)

Broad Institute¹, Massachusetts Institute of Technology²

17 Mar 2005-Nature

TL;DR: In this article, a comparative analysis of the human, mouse, rat and dog genomes is presented to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs).

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Abstract: Comprehensive identification of all functional elements encoded in the human genome is a fundamental need in biomedical research. Here, we present a comparative analysis of the human, mouse, rat and dog genomes to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs). The promoter analysis yields 174 candidate motifs, including most previously known transcription-factor binding sites and 105 new motifs. The 3'-UTR analysis yields 106 motifs likely to be involved in post-transcriptional regulation. Nearly one-half are associated with microRNAs (miRNAs), leading to the discovery of many new miRNA genes and their likely target genes. Our results suggest that previous estimates of the number of human miRNA genes were low, and that miRNAs regulate at least 20% of human genes. The overall results provide a systematic view of gene regulation in the human, which will be refined as additional mammalian genomes become available.

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1,954 citations

Journal Article•DOI•

Estrogen Receptor-α Directs Ordered, Cyclical, and Combinatorial Recruitment of Cofactors on a Natural Target Promoter

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Raphaël Métivier¹, Graziella Penot¹, Michael R Hübner¹, George Reid¹, Heike Brand¹, Martin Kos¹, Frank Gannon¹ - Show less +3 more•Institutions (1)

European Bioinformatics Institute¹

12 Dec 2003-Cell

TL;DR: A comprehensive picture of events resulting in transcriptional activation of a gene is provided, through evaluating the estrogen receptor-alpha (NR3A1) target pS2 gene promoter in MCF-7 cells, which implies that transcriptionalactivation is a cyclical process that requires both activating and repressive epigenetic processes.

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1,473 citations

"Simple Combinations of Lineage-Dete..." refers methods in this paper

...Chromatin Immunoprecipitation Chromatin immunoprecipitation (ChIP) was performed with 10–20 3 10(6) cells essentially as described (Métivier et al., 2003)....
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...Chromatin Immunoprecipitation Chromatin immunoprecipitation (ChIP) was performed with 10–20 3 106 cells essentially as described (Métivier et al., 2003)....
[...]

Journal Article•DOI•

Dynamic Regulation of Nucleosome Positioning in the Human Genome

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Dustin E. Schones¹, Kairong Cui¹, Suresh Cuddapah¹, Tae-Young Roh¹, Artem Barski¹, Zhibin Wang¹, Gang Wei¹, Keji Zhao¹ - Show less +4 more•Institutions (1)

National Institutes of Health¹

07 Mar 2008-Cell

TL;DR: It is found that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding and the first nucleosomes downstream of a start site exhibits differential positioning in active and silent genes.

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1,354 citations

"Simple Combinations of Lineage-Dete..." refers background or methods in this paper

...…positions, DNase hypersensitivity, and mononucleosomal ChIP-Seq for a wide range of histone modifications are available, allowing precise determination of nucleosome positions, chromatin accessibility, and histone modifications (Barski et al., 2007; Boyle et al., 2008; Schones et al., 2008)....
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...In this cell type, genome-wide data for nucleosome positions, DNase hypersensitivity, and mononucleosomal ChIP-Seq for a wide range of histone modifications are available, allowing precise determination of nucleosome positions, chromatin accessibility, and histone modifications (Barski et al., 2007; Boyle et al., 2008; Schones et al., 2008)....
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...MNase-Seq Micrococcal nuclease digest and deep sequencing (MNase-Seq) was essentially performed as described (Schones et al., 2008)....
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...To investigate whether the remodeling of H3K4me1-marked nucleosomes in the group II peaks was consistent with changes in nucleosomal occupancy, we mapped nucleosome positions using MNase-Seq (Schones et al., 2008) in PUER cells at 0 hr and 1 hr after treatment with tamoxifen....
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...(D) Average nucleosome positions centered on induced PU.1 peaks before and after 1 hr tamoxifen treatment as defined by MNase-Seq....
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