5 results on '"Pauli, Florencia"'
Search Results
2. Widespread plasticity in CTCF occupancy linked to DNA methylation.
- Author
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Hao Wang, Maurano, Matthew T., Hongzhu Qu, Varley, Katherine E., Gertz, Jason, Pauli, Florencia, Lee, Kristen, Canfield, Theresa, Weaver, Molly, Sandstrom, Richard, Thurman, Robert E., Kaul, Rajinder, Myers, Richard M., and Stamatoyannopoulos, John A.
- Subjects
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DNA methylation , *GENOMES , *CHROMATIN , *METHYLATION , *CELLS - Abstract
CTCF is a ubiquitously expressed regulator of fundamental genomic processes including transcription, intra- and interchromosomal interactions, and chromatin structure. Because of its critical role in genome function, CTCF binding patterns have long been assumed to be largely invariant across different cellular environments. Here we analyze genome- wide occupancy patterns of CTCF by ChIP-seq in 19 diverse human cell types, including normal primary cells and immortal lines. We observed highly reproducible yet surprisingly plastic genomic binding landscapes, indicative of strong cell-selective regulation of CTCF occupancy. Comparison with massively parallel bisulfite sequencing data indicates that 41% of variable CTCF binding is linked to differential DNA methylation, concentrated at two critical positions within the CTCF recognition sequence. Unexpectedly, CTCF binding patterns were markedly different in normal versus immortal cells, with the latter showing widespread disruption of CTCF binding associated with increased methylation. Strikingly, this disruption is accompanied by up-regulation of CTCF expression, with the result that both normal and immortal cells maintain the same average number of CTCF occupancy sites genome-wide. These results reveal a tight linkage between DNA methylation and the global occupancy patterns of a major sequence-specific regulatory factor. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
3. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.
- Author
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Landt, Stephen G., Marinov, Georgi K., Kundaje, Anshul, Kheradpour, Pouya, Pauli, Florencia, Batzoglou, Serafim, Bernstein, Bradley E., Bickel, Peter, Brown, James B., Cayting, Philip, Yiwen Chen, DeSalvo, Gilberto, Epstein, Charles, Fisher-Aylor, Katherine I., Euskirchen, Ghia, Gerstein, Mark, Gertz, Jason, Hartemink, Alexander J., Hoffman, Michael M., and Iyer, Vishwanath R.
- Subjects
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CHROMATIN , *TRANSCRIPTION factors , *HISTONES , *GENOMICS , *METADATA - Abstract
Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode. org/) portals. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
4. Effects of sequence variation on differential allelic transcription factor occupancy and gene expression.
- Author
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Reddy, Timothy E., Gertz, Jason, Pauli, Florencia, Kucera, Katerina S., Varley, Katherine E., Newberry, Kimberly M., Marinov, Georgi K., Mortazavi, Ali, Williams, Brian A., Song, Lingyun, Crawford, Gregory E., Wold, Barbara, Willard, Huntington F., and Myers, Richard M.
- Subjects
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TRANSCRIPTION factors , *GENOMES , *GENE expression , *CELL lines , *PROTEINS - Abstract
A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this problem, we measured genome-wide differential allelic occupancy of 24 TFs and EP300 in a human lymphoblastoid cell line GM12878. Overall, 5% of human TF binding sites have an allelic imbalance in occupancy. At many sites, TFs clustered in TF-binding hubs on the same homolog in especially open chromatin. While genetic variation in core TF binding motifs generally resulted in large allelic differences in TF occupancy, most allelic differences in occupancy were subtle and associated with disruption of weak or noncanonical motifs. We also measured genome-wide differential allelic expression of genes with and without heterozygous exonic variants in the same cells. We found that genes with differential allelic expression were overall less expressed both in GM12878 cells and in unrelated human cell lines. Comparing TF occupancy with expression, we found strong association between allelic occupancy and expression within 100 bp of transcription start sites (TSSs), and weak association up to 100 kb from TSSs. Sites of differential allelic occupancy were significantly enriched for variants associated with disease, particularly autoimmune disease, suggesting that allelic differences in TF occupancy give functional insights into intergenic variants associated with disease. Our results have the potential to increase the power and interpretability of association studies by targeting functional intergenic variants in addition to protein coding sequences. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
5. Widespread plasticity in CTCF occupancy linked to DNA methylation.
- Author
-
Wang H, Maurano MT, Qu H, Varley KE, Gertz J, Pauli F, Lee K, Canfield T, Weaver M, Sandstrom R, Thurman RE, Kaul R, Myers RM, and Stamatoyannopoulos JA
- Subjects
- Binding Sites genetics, CCCTC-Binding Factor, Cell Line, Chromatin Immunoprecipitation, Cluster Analysis, CpG Islands, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Humans, DNA Methylation, Repressor Proteins metabolism
- Abstract
CTCF is a ubiquitously expressed regulator of fundamental genomic processes including transcription, intra- and interchromosomal interactions, and chromatin structure. Because of its critical role in genome function, CTCF binding patterns have long been assumed to be largely invariant across different cellular environments. Here we analyze genome-wide occupancy patterns of CTCF by ChIP-seq in 19 diverse human cell types, including normal primary cells and immortal lines. We observed highly reproducible yet surprisingly plastic genomic binding landscapes, indicative of strong cell-selective regulation of CTCF occupancy. Comparison with massively parallel bisulfite sequencing data indicates that 41% of variable CTCF binding is linked to differential DNA methylation, concentrated at two critical positions within the CTCF recognition sequence. Unexpectedly, CTCF binding patterns were markedly different in normal versus immortal cells, with the latter showing widespread disruption of CTCF binding associated with increased methylation. Strikingly, this disruption is accompanied by up-regulation of CTCF expression, with the result that both normal and immortal cells maintain the same average number of CTCF occupancy sites genome-wide. These results reveal a tight linkage between DNA methylation and the global occupancy patterns of a major sequence-specific regulatory factor.
- Published
- 2012
- Full Text
- View/download PDF
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