On nucleosome positioning

May 13, 2008

One of the topics I’ve been tracking with some interest lately has been nucleosome positioning. I’m going to briefly highlight some of my recent readings on the subject …

In 2006, Segal published a paper in which they attempted to model and predict positioning based purely on localized sequence signals. In the paper, they compared their model to a number of previously published datasets (mostly low resolution or small sized datasets) in order to claim an accuracy of about 50%. In a later paper, Narlikar et. al. (an independent group from the Segal work) showed that using positioning information, the Segal model, can be informative when looking at the regulatory network.

A couple months ago, I saw Jonathan Widom give a talk in which he discussed the initial results of the follow-up work to Segal’s original model. Since the Segal paper, a number of groups have published larger scale and higher resolution mappings of nucleosome positioning, including the Lee et. al. paper (2007). These datasets have provided larger and better datasets which have been used to improve the models of positioning. While I’ve not yet seen the newer model Widom spoke about published, it looked to contain promising improvements to the original.

An entirely different perspective on nucleosomes has to do with histone dynamics. I’ve written before about some elegant work on Histone Turnover, but recently Shivaswamy et. al. took a different approach to the problem. They compared the positioning of nucleosomes in normal versus heat shock conditions and showed some interesting transcription related changes. They also put forth a model in which some nucleosomes are well positioned with neighboring nucleosomes simply pack in around these well defined ones. I know the authors of this paper and they are interested in exploring nucleosome changes in a variety of conditions.

Two additional perspectives are on the horizon: the effects of individual genes on positioning and the pliability of positioning through evolution. Desiree Tillo gave an interesting talk at the recent CSHL Systems Biology meeting on their follow-up work to Lee et. al. (2007). Namely, they are examining nucleosome positioning in a large number of mutant strains (conditional alleles of essentials and deletions of nonessentials) as well as when yeast are challenged with small molecule inhibitors of histone-modifying enzymes. I am aware of at least two groups who are working on the more evolutionary based perspective, but only in the very early stages.

I am definitely NOT an expert in this field, as my current knowledge stems largely from these papers and a few talks. Currently this field is hot and progress is made quickly …. so I’m probably missing several key papers in the area (Suggestions for reading are welcome). Considering the likely influence of nucleosomes on regulation, it is a topic I will continue to follow with some interest.

Segal, E., Fondufe-Mittendorf, Y., Chen, L., Thastrom, A., Field, Y., Moore, I.K., Wang, J.Z., Widom, J. (2006). A genomic code for nucleosome positioning. Nature, 442(7104), 772-778. DOI: 10.1038/nature04979

Lee, W., Tillo, D., Bray, N., Morse, R.H., Davis, R.W., Hughes, T.R., Nislow, C. (2007). A high-resolution atlas of nucleosome occupancy in yeast. Nature Genetics, 39(10), 1235-1244. DOI: 10.1038/ng2117

Narlikar, L., Gordan, R., Hartemink, A.J. (2007). A Nucleosome-Guided Map of Transcription Factor Binding Sites in Yeast. PLoS Computational Biology, 3(11), e215. DOI: 10.1371/journal.pcbi.0030215

Shivaswamy, S., Bhinge, A., Zhao, Y., Jones, S., Hirst, M., Iyer, V.R. (2008). Dynamic Remodeling of Individual Nucleosomes Across a Eukaryotic Genome in Response to Transcriptional Perturbation. PLoS Biology, 6(3), e65. DOI: 10.1371/journal.pbio.0060065


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