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A computational exploration of gene regulation by nucleosome position

Published: 02 August 2010 Publication History

Abstract

More than two meters of DNA is organized inside a five micrometer nucleus of every human cell. This is accomplished by the wrapping of DNA around protein "spools" (histones) to form nucleosomes. Some DNA sequences are more likely to be organized into nucleosomes than others. Because nucleosomes, not bare DNA, are the substrate for DNA-templated reactions, the position and density of nucleosomes play an important role in these processes (e.g., affecting gene regulation). We used a machine learning tool trained to distinguish nucleosome forming from nucleosome inhibitory DNA sequences. This Support Vector Machine (SVM) was used to evaluate DNA sequence and generate nucleosome occupancy predictions for the entire human genome. We used the resulting scores to characterize DNA-encoded nucleosome positioning signals at specific genomic regions. Scores around protein coding regions, specifically intron-exon boundaries, showed a characteristic nucleosome positioning pattern. Previously these boundaries had been identified using a DNA consensus sequence, and we were able to identify a subset of protein genes based on sequence features recognized by the SVM that are not readily identifiable by traditional sequence evaluation techniques. We anticipate that this type of analysis will allow us to refine our understanding of DNA regulatory processes.

References

[1]
Kornblihtt, A. R., Schor, I. E., Allo, M. and Blencowe, B. J. When chromatin meets splicing. Nat Struct Mol Biol, 16, 9 (Sep 2009), 902--903.
[2]
Kornberg, R. D. and Lorch, Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell, 98, 3 (Aug 6 1999), 285--294.
[3]
Schwartz, S., Meshorer, E. and Ast, G. Chromatin organization marks exon-intron structure. Nat Struct Mol Biol, 16, 9 (Sep 2009), 990--995.
[4]
Tilgner, H., Nikolaou, C., Althammer, S., Sammeth, M., Beato, M., Valcarcel, J. and Guigo, R. Nucleosome positioning as a determinant of exon recognition. Nat Struct Mol Biol, 16, 9 (Sep 2009), 996--1001.
[5]
Luco, R. F., Pan, Q., Tominaga, K., Blencowe, B. J., Pereira-Smith, O. M. and Misteli, T. Regulation of alternative splicing by histone modifications. Science, 327, 5968 (Feb 19, 996--1000.
[6]
Gupta, S., Dennis, J., Thurman, R. E., Kingston, R., Stamatoyannopoulos, J. A. and Noble, W. S. Predicting human nucleosome occupancy from primary sequence. PLoS Comput Biol, 4, 8 2008), e1000134.
[7]
Eden, E., Navon, R., Steinfeld, I., Lipson, D. and Yakhini, Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics, 102009), 48.

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cover image ACM Conferences
BCB '10: Proceedings of the First ACM International Conference on Bioinformatics and Computational Biology
August 2010
705 pages
ISBN:9781450304382
DOI:10.1145/1854776
Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

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Association for Computing Machinery

New York, NY, United States

Publication History

Published: 02 August 2010

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Author Tags

  1. DNA sequence
  2. chromatin
  3. machine learning
  4. nucleosome
  5. support vector machine

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