Role of nucleosome positioning in 3D chromatin organization and loop formation

We present a physics-based polymer model that can investigate 3D organization of chromatin accounting for DNA elasticity,DNA-bending due to nucleosomes, and 1D organization of nucleosomes along DNA. We find that the packing density ofchromatin oscillates between densities corresponding to highly folded and extended configurations as we change thenucleosome organization (length of linker DNA). We compute the looping probability of chromatin and show that thepresence of nucleosomes increases the looping probability of the chain compared to that of a bare DNA. We also show thatlooping probability has a large variability depending on the nature of nucleosome organization and density of linker histones.

ENCODE: A Sourcebook of Epigenomes and Chromatin Language

Until recently, since the Human Genome Project, the general view has been that the majority of the human genome is composed of junk DNA and has little or no selective advantage to the organism. Now we know that this conclusion is an oversimplification. In April 2003, the National Human Genome Research Institute (NHGRI) launched an international research consortium called Encyclopedia of DNA Elements (ENCODE) to uncover non-coding functional elements in the human genome. The result of this project has identified a set of new DNA regulatory elements, based on novel relationships among chromatin accessibility, histone modifications, nucleosome positioning, DNA methylation, transcription, and the occupancy of sequence-specific factors. The project gives us new insights into the organization and regulation of the human genome and epigenome. Here, we sought to summarize particular aspects of the ENCODE project and highlight the features and data that have recently been released. At the end of this review, we have summarized a case study we conducted using the ENCODE epigenome data.

Nucleosome Positioning and RNA Splicing / 生物化学与生物物理进展

Based on the characteristic of nucleotide distribution in nucleosome positioning and inhibiting sequences, the method of Increment of Diversity with Quadratic Discriminant (IDQD) was applied to the classification of these two types of sequences. The mean area under ROC curve archives 0.958. By using this model, the nucleosome formation potential was analyzed in the regions around the splice sites (GT/AG). The results show that coding regions have a high potential to form the nucleosome and the primary RNA transcripts are rigid, while DNA sequences corresponding to the splice sites and their adjacent intron regions tend to be nucleosome free and the primary transcripts from these regions are relative flexible. Moreover, the negative correlation between nucleosome positioning/inhibiting of DNA sequences and RNA flexibility/rigidity is demonstrated around the splice sites, providing a mechanism for understanding the correlation between the nucleosome positioning of DNA and the splicing of transcribed RNA sequences.

Analysis of nucleosome arrangement on satellite DNA of rat liver chromatin.

The arrangement of nucleosomes on the nucleotide sequence of satellite DNA of Oceanian rat (Rattus rattus) has been studied. Nucleosome cores were prepared from rat liver nuclei with micrococcal nuclease, exonuclease III and nuclease Sl. From the total population of core DNA fragments, the satellite-containing fragments were selected by molecular cloning and the complete nucleotide sequence of these clones was determined. The data show that nucleosomes occupy a number of preferred positions on satellite DNA. These positions are strictly defined. Thus location of nucleosomes along the satellite sequence is non-random. Such finding may have important biological significance.