Drosophila Brahma complex remodels nucleosome organizations in multiple aspects.
Bottom Line: The results show that Brm knockdown leads to nucleosome occupancy changes throughout the entire genome with a bias in occupancy decrease.Nucleosome arrays around the 5' ends of genes are reorganized in five patterns as a result of Brm knockdown.Further analyses reveal abundance of AT-rich motifs for transcription factors in the remodeling regions.
Affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai Key Laboratory of Signaling and Disease Research, the School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.Show MeSH
Mentions: The −1, NFR (nucleosome free region), +1, +2, +3, etc. canonical nucleosome arrangement around TSS regions plays an important role in gene transcription regulation and is linked to many biological processes (3,4,22,32,33). To gain insights on how Brm knockdown alters nucleosome profiles around TSS regions, we explored nucleosome organization difference in the regions surrounding TSS. The unsupervised clustering of nucleosome organization changes around TSS regions revealed five distinct patterns (Figure 3). The original composite distribution of nucleosomes around TSS of approximately two-thirds of genes (Cluster I) showed a very similar pattern before and after Brm knockdown. There was only slight shift in +3, +4, +5, etc. downstream nucleosomes and the nucleosomes >500 bp upstream of TSS (Cluster I). In contrast, Brm knockdown resulted in pronounced shift to 3′ end in +3, +4, +5, etc. downstream nucleosomes. The positioning phase of highly phased −1, +1 and +2 nucleosomes remained unchanged (Cluster III). Another pattern of nucleosome profiles showed position shift of nucleosomes nearby 1-kb upstream of TSS (Cluster VI). There was also marked shift of the entire canonical nucleosomes around TSS (−1, +1, +2, +3, +4, +5, etc. nucleosomes). The shift direction was towards 5′ end in a group of genes (Cluster II) and toward 3′ end in the other group of genes (Cluster V). The functional analysis showed that the different classes of genes had the enrichment of distinct GO terms (Supplementary Figure S5). For example, respiratory system development, cell motion, cuticle development, etc. were enriched in Cluster II genes. Oxidation reduction, mesoderm development, gastrulation, etc. were enriched in Cluster V genes.
Affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai Key Laboratory of Signaling and Disease Research, the School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.