Tissue-specific nuclear architecture and gene expression regulated by SATB1.
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.
Cai
Shutao
S
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road (84-171), University of California, Berkeley, California 94720, USA.
Han
Hye-Jung
HJ
Kohwi-Shigematsu
Terumi
T
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016259:Genes, myc; D006657:Histones / Q000235:genetics / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D036961:Matrix Attachment Region Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution
D002843:Chromatin; D006657:Histones; D036961:Matrix Attachment Region Binding Proteins; D009687:Nuclear Proteins; C469541:Satb1 protein, mouse; D004247:DNA