Tissue-specific nuclear architecture and gene expression regulated by SATB1

Nat Genet. 2003 May;34(1):42-51. doi: 10.1038/ng1146.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Nucleus / genetics*
  • Cell Nucleus / metabolism*
  • Chromatin / metabolism
  • DNA / genetics
  • DNA / metabolism
  • Gene Expression Regulation
  • Genes, myc
  • Histones / genetics
  • Histones / metabolism
  • In Situ Hybridization, Fluorescence
  • Matrix Attachment Region Binding Proteins / deficiency
  • Matrix Attachment Region Binding Proteins / genetics*
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Molecular Sequence Data
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • T-Lymphocytes / metabolism
  • Tissue Distribution


  • Chromatin
  • Histones
  • Matrix Attachment Region Binding Proteins
  • Nuclear Proteins
  • Satb1 protein, mouse
  • DNA

Associated data

  • GENBANK/AB046818
  • GENBANK/AC023608
  • GENBANK/AK007869
  • GENBANK/BC018474
  • GENBANK/BC030338
  • GENBANK/M26861
  • GENBANK/P26641
  • RefSeq/NM_002971
  • RefSeq/NM_014805
  • RefSeq/NT_039480
  • RefSeq/NT_039692