ENCODE Data in the UCSC Genome Browser: year 5 update

Rosenbloom, Kate R.; Sloan, Cricket A.; Malladi, Venkat S.; Dreszer, Timothy R.; Learned, Katrina; Kirkup, Vanessa M.; Wong, Matthew C.; Maddren, Morgan; Fang, Ruihua; Heitner, Steven G.; Lee, Brian T.; Barber, Galt P.; Harte, Rachel A.; Diekhans, Mark; Long, Jeffrey C.; Wilder, Steven P.; Zweig, Ann S.; Karolchik, Donna; Kuhn, Robert M.; Haussler, David; Kent, W. James

doi:10.1093/nar/gks1172

Cited by 732 publications

(770 citation statements)

References 25 publications

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“…However, the failure of mouse models to recapitulate this disease is most likely attributable to the observed variation in expression of Sec23a and Sec23b in comparison with their human counterparts. Indeed, analyses of published ChIP-seq data show binding of GATA1 to the proximal promoter region of the Sec23A gene in mouse erythroleukemia cells but not in human K562 cells (41,42). This is only one of several such diseases that fail to be faithfully recapitulated by mouse models (2).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional divergence and conservation of human and mouse erythropoiesis

Pishesha

Thiru

Shi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Mouse models have been instrumental in advancing our understanding of blood cell production. Although many studies have suggested specific differences between human and mouse red cell production (erythropoiesis), a global study of such similarities and differences has been lacking. By computationally comparing global gene expression data from adult human and mouse erythroid precursors representing the distinct stages of maturation, we showed that, while the overall transcriptional landscape has changed, critical erythroid gene signatures and transcriptional regulators have remained conserved. Importantly, these analyses can serve as a tool to integrate data between human and mouse erythropoiesis research, explain why certain human blood diseases are not faithfully recapitulated in mouse models, and highlight hurdles in translating therapeutic findings from mice to humans.

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Section: Discussionmentioning

confidence: 99%

Transcriptional divergence and conservation of human and mouse erythropoiesis

Pishesha

Thiru

Shi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…To identify potential monocyte-specific functional regions of RETN and its flanking region, we examined CTCF binding sites, histone modifications and DNase I peaks previously described for a human monocyte (CD14 + ) sample [33] (ESM Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide association study suggests that SNPs in the promoter region of RETN influence plasma resistin level via effects on DNA methylation at neighbouring sites

et al. 2015

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Aims/hypothesis To investigate epigenetic regulation of the plasma concentration of resistin, we performed an epigenomewide association study for this variable and DNA methylation (DNAm) in an elderly Japanese cohort and then assessed the relation of single nucleotide polymorphisms (SNPs) associated with the plasma resistin concentration to DNAm level at identified sites. Methods The association of plasma resistin level with DNAm status was examined in 191 nondiabetic elderly men with the Illumina Infinium HumanMethylation450 BeadChip array. The association between DNAm status at specific sites in the flanking region of the resistin gene (RETN) and RETN mRNA abundance was then evaluated with a public data set for 1202 monocyte samples from a multi-ethnic cohort. Finally, the association of DNAm status and SNPs in the promoter region of RETN was assessed in two cohorts comprising a total of 478 Japanese individuals.Results DNAm status at cg02346997 located in the RETN promoter region showed a negative genome-wide significant association with the plasma resistin level (p=6.02×10 −10 ). Four DNAm sites in the RETN promoter region including cg02346997 (p=4.23×10 −70 ) showed a negative genome-wide significant association with RETN mRNA abundance in monocytes. Furthermore, the number of minor alleles of the RETN promoter SNPs rs34861192 and rs3219175 was negatively associated with DNAm level at cg02346997 (p=4.43×10 −17 ). Conclusions/interpretation Our results suggest that RETN promoter SNPs might influence the circulating resistin level through an effect on DNAm at cg02346997 and on RETN mRNA abundance in monocytes.

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“…ENCODE DNase-seq peaks (DHS) were downloaded from the UCSC Genome Browser (Rosenbloom et al 2013) (Duke DNase I HS July 2012 freeze) for human genome build hg19. DHS intervals were merged using BEDTools (Quinlan and Hall 2010) (v2.17) and those intersecting a 2-Mb window centered on the MET TSS were clustered and visualized with TreeView (Eisen et al 1998).…”

Section: Dhs Clustering Analysismentioning

confidence: 99%

Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition

et al. 2014

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Thousands of putative enhancers are characterized in the human genome, yet few have been shown to have a functional role in cancer progression. Inhibiting oncokinases, such as EGFR, ALK, ERBB2, and BRAF, is a mainstay of current cancer therapy but is hindered by innate drug resistance mediated by up-regulation of the HGF receptor, MET. The mechanisms mediating such genomic responses to targeted therapy are unknown. Here, we identify lineage-specific enhancers at the MET locus for multiple common tumor types, including a melanoma lineage-specific enhancer 63 kb downstream from the MET TSS. This enhancer displays inducible chromatin looping with the MET promoter to up-regulate MET expression upon BRAF inhibition. Epigenomic analysis demonstrated that the melanocyte-specific transcription factor, MITF, mediates this enhancer function. Targeted genomic deletion (<7 bp) of the MITF motif within the MET enhancer suppressed inducible chromatin looping and innate drug resistance, while maintaining MITF-dependent, inhibitor-induced melanoma cell differentiation. Epigenomic analysis can thus guide functional disruption of regulatory DNA to decouple pro-and antioncogenic functions of a dominant transcription factor and block innate resistance to oncokinase therapy.

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ENCODE Data in the UCSC Genome Browser: year 5 update

Cited by 732 publications

References 25 publications

Transcriptional divergence and conservation of human and mouse erythropoiesis

Transcriptional divergence and conservation of human and mouse erythropoiesis

Epigenome-wide association study suggests that SNPs in the promoter region of RETN influence plasma resistin level via effects on DNA methylation at neighbouring sites

Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition

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