ISWI Regulates Higher-Order Chromatin Structure and Histone H1 Assembly In Vivo

Jim Kadonaga,Davide F V Corona,Stephanie A Mcclymont,Giorgia Siriaco,John W Tamkun,Jennifer A Armstrong,Matthew P Scott,Natalia Snarskaya

doi:10.1371/journal.pbio.0050232

Jim Kadonaga, Davide F V Corona + Show 6 more

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https://doi.org/10.1371/journal.pbio.0050232

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Abstract

Imitation SWI (ISWI) and other ATP-dependent chromatin-remodeling factors play key roles in transcription and other processes by altering the structure and positioning of nucleosomes. Recent studies have also implicated ISWI in the regulation of higher-order chromatin structure, but its role in this process remains poorly understood. To clarify the role of ISWI in vivo, we examined defects in chromosome structure and gene expression resulting from the loss of Iswi function in Drosophila. Consistent with a broad role in transcriptional regulation, the expression of a large number of genes is altered in Iswi mutant larvae. The expression of a dominant-negative form of ISWI leads to dramatic alterations in higher-order chromatin structure, including the apparent decondensation of both mitotic and polytene chromosomes. The loss of ISWI function does not cause obvious defects in nucleosome assembly, but results in a significant reduction in the level of histone H1 associated with chromatin in vivo. These findings suggest that ISWI plays a global role in chromatin compaction in vivo by promoting the association of the linker histone H1 with chromatin.

Highlights

The packaging of DNA into chromatin is critical for the organization and expression of eukaryotic genomes
Genetic studies have shown that Imitation SWI (ISWI) regulates the structure of the male X chromosome, its role in this process has remained unclear
ISWI might regulate the structure of all chromosomes, with the male X chromosome being exquisitely sensitive to the loss of ISWI function

Summary

Introduction

The packaging of DNA into chromatin is critical for the organization and expression of eukaryotic genomes. The basic unit of chromatin structure—the nucleosome—can repress transcription by blocking the access of transcription factors and other regulatory proteins to DNA [1]. Interactions between nucleosomes lead to the formation of 30-nm fibers, which can be further packaged into increasingly compact structures [2,3,4]. The regulation of higher-order chromatin structure is critical for chromosome condensation and segregation during mitosis and meiosis [5,6]. A growing body of evidence suggests that chromatin folding or looping is important for the regulation of enhancer–promoter interactions and the subdivision of chromosomes into discrete functional domains [7]. The molecular mechanisms used to regulate chromatin structure have been the topic of extensive study

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