Nature Genetics34, 42 - 51 (2003)
Published online: 14 April 2003; | doi:10.1038/ng1146
Tissue-specific nuclear architecture and gene expession regulated by SATB1
Shutao Cai, Hye-Jung Han
& Terumi Kohwi-Shigematsu
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road (84-171), University of California, Berkeley, California 94720, USA.
Correspondence should be addressed to Terumi Kohwi-Shigematsu terumiks@lbl.gov
Eukaryotic chromosomes are packaged in nuclei by many orders of folding. Little is known about how higher-order chromatin packaging might affect gene expression. SATB1 is a cell-type specific nuclear protein that recruits chromatin-remodeling factors and regulates numerous genes during thymocyte differentiation. Here we show that in thymocyte nuclei, SATB1 has a cage-like 'network' distribution circumscribing heterochromatin and selectively tethers specialized DNA sequences onto its network. This was shown by fluorescence in situ hybridization on wild-type and Satb1-null thymocytes using in vivo SATB1-bound sequences as probes. Many gene loci, including that of Myc and a brain-specific gene, are anchored by the SATB1 network at specific genomic sites, and this phenomenon is precisely correlated with proper regulation of distant genes. Histone-modification analyses across a gene-enriched genomic region of 70 kb showed that acetylation of histone H3 at Lys9 and Lys14 peaks at the SATB1-binding site and extends over a region of roughly 10 kb covering genes regulated by SATB1. By contrast, in Satb1-null thymocytes, this site is marked by methylation at H3 Lys9. We propose SATB1 as a new type of gene regulator with a novel nuclear architecture, providing sites for tissue-specific organization of DNA sequences and regulating region-specific histone modification.
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