The Annals of Applied Statistics

Change point analysis of histone modifications reveals epigenetic blocks linking to physical domains

Mengjie Chen, Haifan Lin, and Hongyu Zhao

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Histone modification is a vital epigenetic mechanism for transcriptional control in eukaryotes. High-throughput techniques have enabled whole-genome analysis of histone modifications in recent years. However, most studies assume one combination of histone modification invariantly translates to one transcriptional output regardless of local chromatin environment. In this study we hypothesize that the genome is organized into local domains that manifest a similar enrichment pattern of histone modification, which leads to orchestrated regulation of expression of genes with relevant biological functions. We propose a multivariate Bayesian Change Point (BCP) model to segment the Drosophila melanogaster genome into consecutive blocks on the basis of combinatorial patterns of histone marks. By modeling the sparse distribution of histone marks with a zero-inflated Gaussian mixture, our partitions capture local BLOCKs that manifest a relatively homogeneous enrichment pattern of histone marks. We further characterized BLOCKs by their transcription levels, distribution of genes, degree of co-regulation and GO enrichment. Our results demonstrate that these BLOCKs, although inferred merely from histone modifications, reveal a strong relevance with physical domains, which suggest their important roles in chromatin organization and coordinated gene regulation.

Article information

Ann. Appl. Stat., Volume 10, Number 1 (2016), 506-526.

Received: May 2014
Revised: August 2015
First available in Project Euclid: 25 March 2016

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Bayesian change point model Histone modification chromosomal domain


Chen, Mengjie; Lin, Haifan; Zhao, Hongyu. Change point analysis of histone modifications reveals epigenetic blocks linking to physical domains. Ann. Appl. Stat. 10 (2016), no. 1, 506--526. doi:10.1214/16-AOAS905.

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  • Allis, D. (2007). Epigenetics. Cold Spring Harbor Laboratory Press. Cold Spring Harbor, NY.
  • Barry, D. and Hartigan, J. A. (1992). Product partition models for change point problems. Ann. Statist. 20 260–279.
  • Barry, D. and Hartigan, J. A. (1993). A Bayesian analysis for change point problems. J. Amer. Statist. Assoc. 88 309–319.
  • Chen, M., Lin, H. and Zhao, H. (2016). Supplement to “Change point analysis of histone modifications reveals epigenetic blocks linking to physical domains.” DOI:10.1214/16-AOAS905SUPPA, DOI:10.1214/16-AOAS905SUPPB, DOI:10.1214/16-AOAS905SUPPC, DOI:10.1214/16-AOAS905SUPPD, DOI:10.1214/16-AOAS905SUPPE.
  • Chen, D., Zheng, W., Lin, A., Uyhazi, K., Zhao, H. and Lin, H. (2012). Pumilio 1 suppresses multiple activators of p53 to safeguard spermatogenesis. Current Biology 22 420–425.
  • de Wit, E., Braunschweig, U., Greil, F., Bussemaker, H. J. and van Steensel, B. (2008). Global chromatin domain organization of the Drosophila genome. PLoS Genet. 4 e1000045.
  • Duboule, D. (2007). The rise and fall of Hox gene clusters. Development 134 2549–2560.
  • Eaton, M. L., Prinz, J. A., MacAlpine, H. K., Tretyakov, G., Kharchenko, P. V. et al. (2011). Chromatin signatures of the Drosophila replication program. Genome Res. 21 164–174.
  • Erdman, C. and Emerson, J. W. (2008). A fast Bayesian change point analysis for the segmentation of microarray data. Bioinformatics 24 2143–2148.
  • Ernst, J. and Kellis, M. (2010). Discovery and characterization of chromatin states for systematic annotation of the human genome. Nature Biotechnology 28 817–826.
  • Filion, G. J., van Bemmel, J. G., Braunschweig, U., Talhout, W., Kind, J. et al. (2010). Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143 212–224.
  • Hoffman, M. M., Buske, O. J., Wang, J., Weng, Z., Bilmes, J. A. et al. (2012). Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nature Methods 9 473–476.
  • Hon, G., Ren, B. and Wang, W. (2008). ChromaSig: A probabilistic approach to finding common chromatin signatures in the human genome. PLoS Comput. Biol. 4 e1000201, 16.
  • Jaschek, R. and Tanay, A. (2009). Spatial clustering of multivariate genomic and epigenomic information. Research in Computational Molecular Biology 5541 170–183.
  • Keene, J. D. (2007). RNA regulons: Coordination of post-transcriptional events. Nat. Rev. Genet. 8 533–543.
  • Kharchenko, P. V., Alekseyenko, A. A., Schwartz, Y. B., Minoda, A., Riddle, N. C. et al. (2011). Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471 480–485.
  • Khatri, P., Sirota, M. and Butte, A. J. (2012). Ten years of pathway analysis: Current approaches and outstanding challenges. PLoS Comput. Biol. 8 e1002375.
  • Kosak, S. T. and Groudine, M. (2004). Gene order and dynamic domains. Science 306 644–647.
  • Lee, J. M. and Sonnhammer, E. L. L. (2003). Genomic gene clustering analysis of pathways in eukaryotes. Genome Res. 13 875–882.
  • Lian, H., Thompson, W. A., Thurman, R., Stamatoyannopoulos, J. A., Noble, W. S. et al. (2008). Automated mapping of large-scale chromatin structure in ENCODE. Bioinformatics 24(17) 1911–1916.
  • modENCODE Consortium (2010). Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330 1787–1797.
  • Orlando, V. and Paro, R. (1993). Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Cell 75 1187–1198.
  • Pickersgill, H., Kalverda, B., de Wit, E., Talhout, W., Fornerod, M. and van Steensel, B. (2006). Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat. Genet. 38 1005–1014.
  • Riddle, N. C., Minoda, A., Kharchenko, P. V., Alekseyenko, A. A., Schwartz, Y. B. et al. (2011). Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res. 21 147–163.
  • Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M. et al. (2012). Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148 1–15.
  • Sproul, D., Gilbert, N. and Bickmore, W. A. (2005). The role of chromatin structure in regulating the expression of clustered genes. Nat. Rev. Genet. 6 775–781.
  • Thurman, R. E., Day, N., Noble, W. S. and Stamatoyannopoulos, J. A. (2007). Identification of higher-order functional domains in the human ENCODE regions. Genome Res. 17 917–927.
  • Tolhuis, B., de Wit, E., Muijrers, I., Teunissen, H., Talhout, W., van Steensel, B. and van Lohuizen, M. (2006). Genome-wide profiling of PRC1 and PRC2 polycomb chromatin binding in Drosophila melanogaster. Nat. Genet. 38 694–699.
  • Wang, J., Lunyak, V. V. and Jordan, I. K. (2012). Chromatin signature discovery via histone modification profile alignments. Nucleic Acids Res. 40 10642–10656.
  • Yi, G., Sze, S.-H. and Thon, M. R. (2007). Identifying clusters of functionally related genes in genomes. Bioinformatics 23 1053–1060.

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