GeneMerge—post-genomic analysis, data
mining, and hypothesis testing

Castillo-Davis, Cristian I.; Hartl, Daniel L.

doi:10.1093/bioinformatics/btg114

Cited by 262 publications

(208 citation statements)

References 12 publications

(1 reference statement)

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“…A manual analysis of the computation-derived candidates with known identity (18/29) showed that they clustered in six function groups: 1) chromatin structure, 2) transcription/DNA-binding, 3) adhession/ intercellular junction, 4) Ion-channels, 5) signal transduction, and 6) protein transport/ endoplastic reticulum (Table 2). Analysis with a web-based program GeneMerger [33] revealed similar enrichment (2-5 fold) in GO terms, which were statistically significant (see Supplementary Materials, S1), but the classification was not as precise as the manually built list. This result prompted us to compare the computation-derived basonuclin target genes with a list of genes perturbed by basonuclin-deficiency in mouse oocytes.…”

Section: Pathways Perturbed By Basonuclin-deficiency and The Basonuclmentioning

confidence: 99%

Search for basonuclin target genes

Wang

Zhang

Schultz

et al. 2006

Biochemical and Biophysical Research Communications

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Basonuclin (Bnc 1) is a transcription factor that has an unusual ability to interact with promoters of both RNA polymerases I and II. The action of basonuclin is mediated through three pairs of evolutionarily conserved zinc fingers, which produce three DNase I footprints on the promoters of rDNA and the basonuclin gene. Using these DNase footprints, we built a computational model for the basonuclin DNA-binding module, which was used to identify in silico potential RNA polymerase II target genes in the human and mouse promoter databases. The target genes of basonuclin show that it regulates the expression of proteins involved in chromatin structure, transcription/DNAbinding, ion-channels, adhesion/cell-cell junction, signal transduction and intracellular transport. Our results suggest that basonuclin, like MYC, may coordinate transcriptional activities among the three RNA polymerases. But basonuclin regulates a distinctive set of pathways, which differ from that regulated by MYC.

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Section: Pathways Perturbed By Basonuclin-deficiency and The Basonuclmentioning

confidence: 99%

Search for basonuclin target genes

Wang

Zhang

Schultz

et al. 2006

Biochemical and Biophysical Research Communications

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“…Specifically, our studies identify a subset of DLBCLs, the BCR tumors, in which BCL6 plays a critical biological role. The BCR consensus cluster designation was more accurate in predicting BPI sensitivity than Enrichment was evaluated using the GeneMerge program (18), which compares the frequency of GO categories represented in the nonredundant list of SwissProt/TrEMBL accession nos. of BCL6 target genes (n ϭ 418) versus the global frequency of GO categories in the population gene file [19,168 nonredundant SwissProt/TrEMBL accession nos.…”

Section: Bcl6 Actively Represses Its Target Genes In Bcr But Not Oxphosmentioning

confidence: 99%

“…GO enrichment analysis was carried out with GO biological process terms, and obtained P values were corrected for multiple-hypothesis testing by false-discovery rate (FDR) (24,25). P values (E scores) for GO term overrepresentation in the BCL6 target genes were obtained using the hypergeometric distribution (18,29). The hypergeometric distribution quantifies the overrepresentation of a given GO term in a sample of a specific size that is drawn from a larger population (18).…”

Section: Bcl6 Actively Represses Its Target Genes In Bcr But Not Oxphosmentioning

confidence: 99%

“…P values (E scores) for GO term overrepresentation in the BCL6 target genes were obtained using the hypergeometric distribution (18,29). The hypergeometric distribution quantifies the overrepresentation of a given GO term in a sample of a specific size that is drawn from a larger population (18).…”

Section: Bcl6 Actively Represses Its Target Genes In Bcr But Not Oxphosmentioning

confidence: 99%

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Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas

Polo

Juszczyński

Monti

et al. 2007

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

130

172

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Diffuse large B cell lymphomas (DLBCLs) often express BCL6, a transcriptional repressor required for the formation of normal germinal centers. In a subset of DLBCLs, BCL6 is deregulated by chromosomal translocations or aberrant somatic hypermutation; in other tumors, BCL6 expression may simply reflect germinal center lineage. DLBCLs dependent on BCL6-regulated pathways should exhibit differential regulation of BCL6 target genes. Genomic array ChIP-on-chip was used to identify the cohort of direct BCL6 target genes. This set of genes was enriched in modulators of transcription, chromatin structure, protein ubiquitylation, cell cycle, and DNA damage responses. In primary DLBCLs classified on the basis of gene expression profiles, these BCL6 target genes were clearly differentially regulated in ''BCR'' tumors, a subset of DLBCLs with increased BCL6 expression and more frequent BCL6 translocations. In a panel of DLBCL cell lines analyzed by expression arrays and classified according to their gene expression profiles, only BCR tumors were highly sensitive to the BCL6 peptide inhibitor, BPI. These studies identify a discrete subset of DLBCLs that are reliant on BCL6 signaling and uniquely sensitive to BCL6 inhibitors. More broadly, these data show how genome-wide identification of direct target genes can identify tumors dependent on oncogenic transcription factors and amenable to targeted therapeutics.targeted therapy ͉ transcriptional repression ͉ ChIP on ChIP ͉ integrative analysis ͉ gene expression profiling B CL6 is a BTB/POZ domain transcription repressor that is required for normal germinal center (GC) development and expressed by the majority of normal GC B cells and a subset of diffuse large B cell lymphomas (DLBCLs) (1, 2). BCL6 favors the survival and proliferation of GC B cells, which undergo somatic hypermutation of Ig variable regions and Ig class switch recombination; down-regulation of BCL6 is necessary for post-GC B cell maturation (3-5). Deregulation of BCL6, by chromosomal translocation or aberrant somatic hypermutation, is the most common genetic abnormality in DLBCL (6). Conclusive evidence for the oncogenic role of BCL6 comes from murine models in which constitutive BCL6 expression results in the development of a lymphoid malignancy resembling DLBCL (7,8). Although deregulated BCL6 clearly plays a pathogenetic role in a subset of human DLBCLs, other DLBCLs may simply express this transcriptional repressor because the lymphomas are derived from normal BCL6 ϩ GC B cells. Identification of BCL6-dependent tumors has important therapeutic implications because a recently described specific BCL6 peptide inhibitor (BPI) inhibits the growth of some but not all DLBCLs (9).To delineate functionally relevant DLBCL subsets, we and others have used gene expression signatures. In an earlier approach known as the cell of origin (COO) classification, subsets of DLBCLs were associated with specific types of normal B cells [GC B cells (GCB) or in vitro activated peripheral blood B cells (ABC)] or left unassigned if ...

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“…A possible formation of HSF2-binding clusters was studied through the chromosomal distribution of target genes by using the GeneMerge analysis tool (18). To our surprise, a profound accumulation of HSF2 targets was detected on the Y chromosome, in comparison to the total amount of promoters per chromosome on the microarray (Table 1).…”

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confidence: 98%

Promoter ChIP-chip analysis in mouse testis reveals Y chromosome occupancy by HSF2

Åkerfelt

Henriksson

Laiho

et al. 2008

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

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The mammalian Y chromosome is essential for spermatogenesis, which is characterized by sperm cell differentiation and chromatin condensation for acquisition of correct shape of the sperm. Deletions of the male-specific region of the mouse Y chromosome long arm (MSYq), harboring multiple copies of a few genes, lead to sperm head defects and impaired fertility. Using chromatin immunoprecipitation on promoter microarray (ChIP-chip) on mouse testis, we found a striking in vivo MSYq occupancy by heat shock factor 2 (HSF2), a transcription factor involved in spermatogenesis. HSF2 was also found to regulate the transcription of MSYq resident genes, whose transcriptional regulation has been unknown. Importantly, disruption of Hsf2 caused a similar phenotype as the 2/3 deletion of MSYq, i.e., altered expression of the multicopy genes and increased mild sperm head abnormalities. Consequently, aberrant levels of chromatin packing proteins and more frequent DNA fragmentation were detected, implying that HSF2 is required for correct chromatin organization in the sperm. Our findings define a physiological role for HSF2 in the regulation of MSYq resident genes and the quality of sperm. chromatin packing ͉ heat shock factor ͉ MSYq ͉ promoter microarray ͉ spermatogenesis

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GeneMerge—post-genomic analysis, data mining, and hypothesis testing

Abstract: GeneMerge is available free of charge for academic use over the web and for download from: http://www.oeb.harvard.edu/hartl/lab/publications/GeneMerge.html.

Cited by 262 publications

References 12 publications

Search for basonuclin target genes

Search for basonuclin target genes

Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas

Promoter ChIP-chip analysis in mouse testis reveals Y chromosome occupancy by HSF2

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