Abstract
dMi-2 is a highly conserved ATP-dependent chromatin-remodeling factor that regulates transcription and cell fates by altering the structure or positioning of nucleosomes. Here we report an unanticipated role for dMi-2 in the regulation of higher-order chromatin structure in Drosophila. Loss of dMi-2 function causes salivary gland polytene chromosomes to lose their characteristic banding pattern and appear more condensed than normal. Conversely, increased expression of dMi-2 triggers decondensation of polytene chromosomes accompanied by a significant increase in nuclear volume; this effect is relatively rapid and is dependent on the ATPase activity of dMi-2. Live analysis revealed that dMi-2 disrupts interactions between the aligned chromatids of salivary gland polytene chromosomes. dMi-2 and the cohesin complex are enriched at sites of active transcription; fluorescence-recovery after photobleaching (FRAP) assays showed that dMi-2 decreases stable association of cohesin with polytene chromosomes. These findings demonstrate that dMi-2 is an important regulator of both chromosome condensation and cohesin binding in interphase cells.
Highlights
The packaging of DNA into chromatin is critical for the organization and expression of eukaryotic genes [1,2,3]
Using Drosophila as a model organism, we have discovered an unanticipated role for Drosophila Mi-2 (dMi-2), a well-characterized ATP-dependent chromatin-remodeling factor, in the regulation of higher-order chromatin structure and cohesin dynamics in vivo
Our findings suggest that dMi-2 may regulate transcription and cellular differentiation in other organisms, including humans, by altering higher-order chromatin structure or cohesin dynamics
Summary
The packaging of DNA into chromatin is critical for the organization and expression of eukaryotic genes [1,2,3]. The basic unit of chromatin structure, the nucleosome, contains the core histones H2A, H2B, H3 and H4. The association of nucleosomes with histone H1 and other linker histones facilitates their packaging into 30 nm fibers, which in turn are packaged into increasingly compact higher-order structures. There is growing evidence that levels of chromosome organization above the level of the nucleosome – including chromosome folding, pairing and looping – play important roles in the regulation of gene expression. Condensin and cohesin, which were initially identified by their roles in mitosis and meiosis, modulate transcription by promoting long-range chromosomal interactions and DNA looping in interphase cells [4]
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