Man Yu
University of Washington
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Featured researches published by Man Yu.
Nature Methods | 2006
Peter J. Sabo; Michael S. Kuehn; Robert A F Thurman; Brett E. Johnson; Ericka M. Johnson; Hua Cao; Man Yu; Elizabeth Rosenzweig; Jeff Goldy; Andrew K. Haydock; M. B. Weaver; Anthony Shafer; Kristin Lee; Fidencio Neri; Richard Humbert; Michael A. Singer; Todd Richmond; Michael O. Dorschner; Michael McArthur; Michael Hawrylycz; Roland D. Green; Patrick A. Navas; William Stafford Noble; John A. Stamatoyannopoulos
Localized accessibility of critical DNA sequences to the regulatory machinery is a key requirement for regulation of human genes. Here we describe a high-resolution, genome-scale approach for quantifying chromatin accessibility by measuring DNase I sensitivity as a continuous function of genome position using tiling DNA microarrays (DNase-array). We demonstrate this approach across 1% (∼30 Mb) of the human genome, wherein we localized 2,690 classical DNase I hypersensitive sites with high sensitivity and specificity, and also mapped larger-scale patterns of chromatin architecture. DNase I hypersensitive sites exhibit marked aggregation around transcriptional start sites (TSSs), though the majority mark nonpromoter functional elements. We also developed a computational approach for visualizing higher-order features of chromatin structure. This revealed that human chromatin organization is dominated by large (100–500 kb) superclusters of DNase I hypersensitive sites, which encompass both gene-rich and gene-poor regions. DNase-array is a powerful and straightforward approach for systematic exposition of the cis-regulatory architecture of complex genomes.
intelligent systems in molecular biology | 2005
William Stafford Noble; Scott Kuehn; Robert E. Thurman; Man Yu; John A. Stamatoyannopoulos
MOTIVATIONnIn the living cell nucleus, genomic DNA is packaged into chromatin. DNA sequences that regulate transcription and other chromosomal processes are associated with local disruptions, or openings, in chromatin structure caused by the cooperative action of regulatory proteins. Such perturbations are extremely specific for cis-regulatory elements and occur over short stretches of DNA (typically approximately 250 bp). They can be detected experimentally as DNaseI hypersensitive sites (HSs) in vivo, though the process is extremely laborious and costly. The ability to discriminate DNaseI HSs computationally would have a major impact on the annotation and utilization of the human genome.nnnRESULTSnWe found that a supervised pattern recognition algorithm, trained using a set of 280 DNaseI HS and 737 non-HS control sequences from erythroid cells, was capable of de novo prediction of HSs across the human genome with surprisingly high accuracy determined by prospective in vivo validation. Systematic application of this computational approach will greatly facilitate the discovery and analysis of functional non-coding elements in the human and other complex genomes.nnnAVAILABILITYnSupplementary data is available at noble.gs.washington.edu/proj/hs
Molecular and Cellular Biology | 2005
Xiangdong Fang; Jin Sun; Ping Xiang; Man Yu; Patrick A. Navas; Kenneth R. Peterson; George Stamatoyannopoulos; Qiliang Li
ABSTRACT Deletion of the 234-bp core element of the DNase I hypersensitive site 3 (5′HS3) of the locus control region (LCR) in the context of a human beta-globin locus yeast artificial chromosome (β-YAC) results in profound effects on globin gene expression in transgenic mice. In contrast, deletion of a 2.3-kb 5′HS3 region, which includes the 234-bp core sequence, has a much milder phenotype. Here we report the effects of these deletions on chromatin structure in the beta-globin locus of adult erythroblasts. The 234-bp 5′HS3 deletion abolished histone acetylation throughout the β-globin locus; recruitment of RNA polymerase II (pol II) to the LCR and beta-globin gene promoter was reduced to a basal level; and formation of all the 5′ DNase I hypersensitive sites of the LCR was disrupted. The 2.3-kb 5′HS3 deletion mildly reduced the level of histone acetylation but did not change the profile across the whole locus; the 5′ DNase I hypersensitive sites of the LCR were formed, but to a lesser extent; and recruitment of pol II was reduced, but only marginally. These data support the hypothesis that the LCR forms a specific chromatin structure and acts as a single entity. Based on these results we elaborate on a model of LCR chromatin architecture which accommodates the distinct phenotypes of the 5′HS3 and HS3 core deletions.
Molecular and Cellular Biology | 2006
Man Yu; Hemei Han; Ping Xiang; Qiliang Li; George Stamatoyannopoulos
ABSTRACT To investigate the control of the γ-globin gene during development, we produced transgenic mice in which sequences of the β-gene promoter were replaced by equivalent sequences of the γ-gene promoter in the context of a human β-globin locus yeast artificial chromosome (βYAC) and analyzed the effects on globin gene expression during development. Replacement of 1,077 nucleotides (nt) of the β-gene promoter by 1,359 nt of the γ promoter resulted in striking inhibition of the γ-promoter/β-gene expression in the adult stage of development, providing direct evidence that the expression of the γ gene in the adult is mainly controlled by autonomous silencing. Measurements of the expression of the γ promoter/β-globin gene as well as the wild γ genes showed that gene competition is also involved in the control of γ-gene expression in the fetal stage of development. We conclude that autonomous silencing is the main mechanism controlling γ-gene expression in the adult, while autonomous silencing as well as competition between γ and β genes contributes to the control of γ to β switching during fetal development.
Nucleic Acids Research | 2006
Qiliang Li; Xiangdong Fang; Ivan Olave; Hemei Han; Man Yu; Ping Xiang; George Stamatoyannopoulos
To test the role of CACCC box on γ-globin gene activation, the CACCC box was deleted or mutated and γ-gene expression was monitored in transgenic mice. Disruption of the CACCC box had no effect on γ-gene expression in the cells of embryonic erythropoiesis but it strikingly reduced γ-gene expression in fetal erythropoiesis, and abolished γ-gene expression in adult erythroid cells. The CACCC mutation diminished HS formation, as well as TBP and polII recruitment at the γ-gene promoter; however, it only resulted in slight or no effects on histone H3 and H4 acetylation in adult erythropoiesis. Our findings indicate that each basic cis element of the proximal γ-gene promoter, i.e. CACCC, CCAAT or TATA box, can be disrupted without affecting the activation of γ gene in embryonic erythroid cells. We propose that the trans factors recruited by the three boxes interact with each other to form a ‘promoter complex’. In embryonic erythropoiesis the locus control region enhancer is able to interact with the complex even when components normally binding to one of the motifs are missing, but it can only activate an intact ‘promoter complex’ in adult erythroid cells.
Proceedings of the National Academy of Sciences of the United States of America | 2004
Peter J. Sabo; Michael Hawrylycz; James C. Wallace; Richard Humbert; Man Yu; Anthony Shafer; Janelle Kawamoto; Robert O. Hall; Joshua Mack; Michael O. Dorschner; Michael McArthur; John A. Stamatoyannopoulos
Blood | 2005
Qiliang Li; David W. Emery; Hemei Han; Jin Sun; Man Yu; George Stamatoyannopoulos
Human Molecular Genetics | 2003
Patrick A. Navas; Richard A Swank; Man Yu; Kenneth R. Peterson; George Stamatoyannopoulos
Blood Cells Molecules and Diseases | 2005
Man Yu; Qiliang Li; George Stamatoyannopoulos
Blood | 2004
Man Yu; Xin Ye; Hemei Han; Mary Stafford; Patrick A. Navas; Qiliang Li; George Stamatoyannopoulos