Model-based analysis of tiling-arrays for ChIP-chip

Johnson, W. Evan; Li, Wei; Meyer, Clifford A.; Gottardo, Raphaël; Carroll, Jason S.; Brown, Myles; Liu, X. Shirley

doi:10.1073/pnas.0601180103

Cited by 388 publications

(439 citation statements)

References 15 publications

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“…S1C). Three biological replicates for PPAR␥ and control IgG were hybridized to the wholegenome Mouse Tiling 2.0R Array Set (Affymetrix), and the data were analyzed using the model-based analysis of tiling arrays (MAT) Johnson et al 2006), using the cutoffs of false discovery rate Յ1% and enrichment of PPAR␥ signal over IgG equal to or greather than twofold. This analysis identified 5299 unique regions of ∼1000-base-pair (bp) length, including known sites at Fabp4/aP2, Cd36, Lipe/Hsl, Olr1, and Me1 (Supplemental Table 1).…”

Section: Identification and Validation Of Novel Ppar␥-binding Sitesmentioning

confidence: 99%

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PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

Lefterova¹,

Zhang²,

Steger³

et al. 2008

Genes Dev.

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732

693

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Peroxisome proliferator-activated receptor ␥(PPAR␥), a nuclear receptor and the target of anti-diabetic thiazolinedione drugs, is known as the master regulator of adipocyte biology. Although it regulates hundreds of adipocyte genes, PPAR␥ binding to endogenous genes has rarely been demonstrated. Here, utilizing chromatin immunoprecipitation (ChIP) coupled with whole genome tiling arrays, we identified 5299 genomic regions of PPAR␥ binding in mouse 3T3-L1 adipocytes. The consensus PPAR␥/RXR␣ "DR-1"-binding motif was found at most of the sites, and ChIP for RXR␣ showed colocalization at nearly all locations tested. Bioinformatics analysis also revealed CCAAT/enhancer-binding protein (C/EBP)-binding motifs in the vicinity of most PPAR␥-binding sites, and genome-wide analysis of C/EBP␣ binding demonstrated that it localized to3350 of the locations bound by PPAR␥. Importantly, most genes induced in adipogenesis were bound by both PPAR␥ and C/EBP␣, while very few were PPAR␥-specific. C/EBP␤ also plays a role at many of these genes, such that both C/EBP␣ and ␤ are required along with PPAR␥ for robust adipocyte-specific gene expression. Thus, PPAR␥ and C/EBP factors cooperatively orchestrate adipocyte biology by adjacent binding on an unanticipated scale.[Keywords: PPAR␥; C/EBP; adipocyte; genome wide; ChIP-chip] Supplemental material is available at http://www.genesdev.org.

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Section: Identification and Validation Of Novel Ppar␥-binding Sitesmentioning

confidence: 99%

“…Whole-genome arrays were analyzed with MAT (Johnson et al 2006), with probes remapped to the February 2006 Mouse Genome Assembly (mm8) using xMAN . The threshold cutoffs for binding regions were FDR Յ1%, and enrichment of PPAR␥ or C/EBP␣ over IgG twofold or more.…”

Section: Chip-chip Analysismentioning

confidence: 99%

PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

Lefterova¹,

Zhang²,

Steger³

et al. 2008

Genes Dev.

Self Cite

732

693

View full text Add to dashboard Cite

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“…To analyze the D-REAM microarray data, we applied modelbased analysis of tiling arrays (MAT) (Johnson et al 2006). MATscores represent the enrichment of unmethylated fragments and are indicative of the relative methylation status of the HpyCH4IV site.…”

Section: Features Of T-dmr Profiling By Restriction Tag-mediated Amplmentioning

confidence: 99%

“…To satisfy gene ID requirements of the bioinformatics analysis, we converted gene IDs under certain circumstances. MAT (Johnson et al 2006) (bandwidth, 300 bp) was used to analyze the tiling array .CEL files and identify the hypomethylated regions based on tiling probe signals, probe sequences, and copy numbers. xMAN (Li et al 2008) was used to remap the original tiling probes according to the mouse genome assembly of version mm8 (March 2006 build) from the UCSC genome database (Kuhn et al 2007).…”

Section: Bioinformaticsmentioning

confidence: 99%

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

et al. 2008

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DNA methylation constitutes an important epigenetic regulation mechanism in many eukaryotes, although the extent of DNA methylation in the regulation of gene expression in the mammalian genome is poorly understood. We developed D-REAM, a genome-wide DNA methylation analysis method for tissue-dependent and differentially methylated region (T-DMR) profiling with restriction tag-mediated amplification in mouse tissues and cells. Using a mouse promoter tiling array covering a region from −6 to 2.5 kb (∼30,000 transcription start sites), we found that over 3000 T-DMRs are hypomethylated in liver compared to cerebrum. The DNA methylation profile of liver was distinct from that of kidney and spleen. This hypomethylation profile marked genes that are specifically expressed in liver, including key transcription factors such as Hnf1a and Hnf4a. Genes with T-DMRs, especially those lacking CpG islands and those with HNF-1A binding motifis in their promoters, showed good correlation between their tissue-specific expression and liver hypomethylation status. T-DMRs located downstream from their transcription start sites also showed tissue-specific gene expression. These data indicate that multilayered regulation of tissue-specific gene function could be elucidated by DNA methylation tissue profiling.

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“…Historically, analysis of NR transcriptional activity has focused on the contributions of chromatin remodeling and assembly of the pre-initiation complex; however, clear roles for remodeling complexes in processes, such as elongation, termination, splicing as well as heterochromatin assembly, suggest a potentially larger field of study must be considered (Horn and Peterson, 2006;Sims et al, 2004;Corey et al, 2003;Batsche et al, 2006;Alen et al, 2002;Morillon et al, 2003). Finally, numerous microarray and chip-on-chip data sets clearly point to various classes of hormonally responsive genes that will be dependent on promoter specificity and biological content for a final transcriptional disposition (Wang et al, 2004;Johnson et al, 2006;Wan and Nordeen, 2003). To this end, the clear mechanistic insights gained from functional interactions between ATP-dependent chromatin remodeling machines and nuclear receptors may provide a way forward to better understand the precise sequence of events involved in transcriptional activation.…”

Section: Discussionmentioning

confidence: 99%

Nuclear receptors and chromatin remodeling machinery

Trotter

Archer

2007

Molecular and Cellular Endocrinology

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Eukaryotic genetic information is stored within the association of DNA and histone proteins resulting in a dynamic polymer called chromatin. The fundamental structural unit of chromatin is the nucleosome which consists of ~146 bp of DNA wrapped around an octamer of histones containing two copies each of four core histones, H2A, H2B, H3 and H4. It is this DNA/protein fiber that transcription factors and other agents of chromatin metabolism must access and regulate. We have developed model systems to study the mechanisms by which steroid receptors control physiological activities by regulating gene expression within a higher order chromatin organization. Our studies have focused on the glucocorticoid receptor and its ability to remodel chromatin which is mediated by the BRG1 complex. Using novel cell systems, we demonstrate that GR-mediated transactivation from chromatin templates requires BRG1 remodeling activity and that other ATP-dependent remodeling proteins cannot substitute for this activity.

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Model-based analysis of tiling-arrays for ChIP-chip

Cited by 388 publications

References 15 publications

PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

Nuclear receptors and chromatin remodeling machinery

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