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Tissue-specific nuclear architecture and gene expession regulated by SATB1

Nature Genetics volume 34, pages 42–51 (2003)Cite this article

Abstract

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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Figure 1: Identification of a cage-like network structure of SATB1 in thymocytes.
Figure 2: SATB1 actively anchors the Myc upstream sequence onto its network.
Figure 3: SATB1 regulates Myc in thymocytes.
Figure 4: Isolation and characterization of individual genomic sequences that bind to SATB1 in vivo in mouse thymocytes.
Figure 5: SATB1 regulates expression of distant genes.
Figure 6: SATB1 creates a chromatin domain marked by specific histone modification.

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Acknowledgements

We thank A. Dernburg for help in obtaining the DeltaVision image, P. Varga-Weisz for valuable discussion and J.-F. Cheng and M. Kohwi for critically reading the manuscript. This work was supported by US National Institutes of Health grants to T.K.-S.

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  1. Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road (84-171), University of California, Berkeley, 94720, California, USA

    Shutao Cai, Hye-Jung Han & Terumi Kohwi-Shigematsu

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Correspondence to Terumi Kohwi-Shigematsu.

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Cai, S., Han, HJ. & Kohwi-Shigematsu, T. Tissue-specific nuclear architecture and gene expession regulated by SATB1. Nat Genet 34, 42–51 (2003). https://doi.org/10.1038/ng1146

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