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Journal ArticleDOI

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

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.
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.
Citations
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Journal ArticleDOI
TL;DR: A simple and robust plate-based single-cell ATAC-seq method that works in fresh and cryopreserved cells and identifies distinct immune cell types and reveal cell type-specific regulatory regions and related transcription factors is developed.
Abstract: The assay for transposase-accessible chromatin using sequencing (ATAC-seq) is widely used to identify regulatory regions throughout the genome. However, very few studies have been performed at the single cell level (scATAC-seq) due to technical challenges. Here we developed a simple and robust plate-based scATAC-seq method, combining upfront bulk Tn5 tagging with single-nuclei sorting. We demonstrate that our method works robustly across various systems, including fresh and cryopreserved cells from primary tissues. By profiling over 3000 splenocytes, we identify distinct immune cell types and reveal cell type-specific regulatory regions and related transcription factors. ATAC-seq is widely used to identify regulatory regions in the genome. Here the authors develop a simple and robust plate-based single-cell ATAC-seq method that works in fresh and cryopreserved cells.

1,260 citations

Journal ArticleDOI
TL;DR: The findings provide the direct evidence that m(6)A reader YTHDC1 regulates mRNA splicing through recruiting and modulating pre-mRNA splicing factors for their access to the binding regions of targeted mRNAs.

1,244 citations

Journal ArticleDOI
TL;DR: An overview of enhancer-associated modifications of histones and DNA is given and enzymatic activities involved in their dynamic deposition and removal are discussed and potential downstream effectors of these marks are described.

1,215 citations

Journal ArticleDOI
19 Oct 2012-Science
TL;DR: The transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver is interrogated and a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II recruitment, RNA expression, and chromatin states is found.
Abstract: The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression, and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.

1,184 citations

Journal ArticleDOI
01 Nov 2018-Cell
TL;DR: The study of immune cell transcriptomes from tumors demonstrates a strategy for identifying predictors, mechanisms, and targets for enhancing checkpoint immunotherapy by targeting novel combinations of factors in exhausted cells.

1,162 citations


Additional excerpts

  • ...…josh/biophysicsweb/ GOMER/index.html CIS-BP database (Weirauch et al., 2014) http://cisbp.ccbr.utoronto.ca/ HOMER version 4.9 (Heinz et al., 2010) http://homer.ucsd.edu/homer/download.html edgeR 3.14.0 (Robinson et al., 2010)…...

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References
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Journal ArticleDOI
18 May 2007-Cell
TL;DR: High-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology are generated.

6,488 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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  • ...1 Binding Programs in Macrophages and B Cells We initially performed chromatin immunoprecipitation-coupled deep sequencing (ChIP-Seq) (Barski et al., 2007) to define the PU....

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  • ..., 2008), human CD4 T cells (Barski et al., 2007), and CD36 erythrocyte precursors (Cui et al....

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  • ...…other cell types, we performed de novo motif analysis on H3K4me1/H3K4me3 ChIP-Seq data sets from mouse embryonic stem cells (Meissner et al., 2008; Mikkelsen et al., 2007), liver (Wederell et al., 2008), human CD4+ T cells (Barski et al., 2007), and CD36+ erythrocyte precursors (Cui et al., 2009)....

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Journal ArticleDOI
02 Aug 2007-Nature
TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
Abstract: We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences Lysine 4 and lysine 9 trimethylation marks imprinting control regions Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations

4,166 citations


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

  • ...To determine whether there is an analogous relationship between promoter-distal H3K4me1 and binding sites for transcription factors in other cell types, we performed de novo motif analysis on H3K4me1/H3K4me3 ChIP-Seq data sets from mouse embryonic stem cells (Meissner et al., 2008; Mikkelsen et al., 2007), liver (Wederell et al....

    [...]

  • ...…other cell types, we performed de novo motif analysis on H3K4me1/H3K4me3 ChIP-Seq data sets from mouse embryonic stem cells (Meissner et al., 2008; Mikkelsen et al., 2007), liver (Wederell et al., 2008), human CD4+ T cells (Barski et al., 2007), and CD36+ erythrocyte precursors (Cui et al., 2009)....

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Journal ArticleDOI
06 Mar 1992-Cell
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.

2,821 citations


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

  • ...…in B lineage progenitors devoid of both E2A and EBF (E2A / ), EBF only (EBF / ), or control cells that express both factors (Rag1 / ), which are arrested at successive stages in B cell development (Dias et al., 2008; Ikawa et al., 2004; Lin and Grosschedl, 1995; Mombaerts et al., 1992) (Figure 1A)....

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  • ...We addressed this question in B lineage progenitors devoid of both E2A and EBF (E2A / ), EBF only (EBF / ), or control cells that express both factors (Rag1 / ), which are arrested at successive stages in B cell development (Dias et al., 2008; Ikawa et al., 2004; Lin and Grosschedl, 1995; Mombaerts et al., 1992) (Figure 1A)....

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Journal ArticleDOI
13 Jun 2008-Cell
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.

2,519 citations


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

  • ...This model offers an explanation for the extensive genome-wide and cell typespecific colocalization of transcription factors observed in various previous studies (Chen et al., 2008; MacArthur et al., 2009) and provides insights into how simple combinations of lineage-restricted transcription factors on a genome-wide scale can specify promoter-distal cis-regulatory elements ultimately responsible for both cell identity and cell type-specific responses to diverse signaling inputs....

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  • ...…an explanation for the extensive genome-wide and cell typespecific colocalization of transcription factors observed in various previous studies (Chen et al., 2008; MacArthur et al., 2009) and provides insights into how simple combinations of lineage-restricted transcription factors on a…...

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  • ...Comparisons of the genome-wide binding patterns of different transcription factors in a variety of species and cell types have generated two major insights regarding transcription factor binding patterns: (1) different factors in the same cell type tend to colocalize on a genome-wide scale (Chen et al., 2008; MacArthur et al., 2009), and (2) the same factor in different cell types or at different stages of development exhibits different genome-wide binding patterns (Lupien et al....

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  • ...…insights regarding transcription factor binding patterns: (1) different factors in the same cell type tend to colocalize on a genome-wide scale (Chen et al., 2008; MacArthur et al., 2009), and (2) the same factor in different cell types or at different stages of development exhibits different…...

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Journal ArticleDOI
07 Aug 2008-Nature
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.
Abstract: DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput reduced representation bisulphite sequencing and single-molecule-based sequencing, we generated DNA methylation maps covering most CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse embryonic stem cells, embryonic-stem-cell-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of embryonic-stem-cell-derived and primary cells reveals that 'weak' CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumours. More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.

2,482 citations


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

  • ...To determine whether there is an analogous relationship between promoter-distal H3K4me1 and binding sites for transcription factors in other cell types, we performed de novo motif analysis on H3K4me1/H3K4me3 ChIP-Seq data sets from mouse embryonic stem cells (Meissner et al., 2008; Mikkelsen et al., 2007), liver (Wederell et al....

    [...]

  • ...…factors in other cell types, we performed de novo motif analysis on H3K4me1/H3K4me3 ChIP-Seq data sets from mouse embryonic stem cells (Meissner et al., 2008; Mikkelsen et al., 2007), liver (Wederell et al., 2008), human CD4+ T cells (Barski et al., 2007), and CD36+ erythrocyte…...

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