SATB1 targets chromatin remodelling to regulate genes over long distances.
Eukaryotic chromosomes are organized inside the nucleus in such a way that only a subset of the genome is expressed in any given cell type, but the details of this organization are largely unknown. SATB1 ('special AT-rich sequence binding 1'), a protein found predominantly in thymocytes, regulates genes by folding chromatin into loop domains, tethering specialized DNA elements to an SATB1 network structure. Ablation of SATB1 by gene targeting results in temporal and spatial mis-expression of numerous genes and arrested T-cell development, suggesting that SATB1 is a cell-type specific global gene regulator. Here we show that SATB1 targets chromatin remodelling to the IL-2Ralpha ('interleukin-2 receptor alpha') gene, which is ectopically transcribed in SATB1 null thymocytes. SATB1 recruits the histone deacetylase contained in the NURD chromatin remodelling complex to a SATB1-bound site in the IL-2Ralpha locus, and mediates the specific deacetylation of histones in a large domain within the locus. SATB1 also targets ACF1 and ISWI, subunits of CHRAC and ACF nucleosome mobilizing complexes, to this specific site and regulates nucleosome positioning over seven kilobases. SATB1 defines a class of transcriptional regulators that function as a 'landing platform' for several chromatin remodelling enzymes and hence regulate large chromatin domains.
Yasui
Dag
D
Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.
Miyano
Masaru
M
Cai
Shutao
S
Varga-Weisz
Patrick
P
Kohwi-Shigematsu
Terumi
T
D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry / Q000502:physiology*; D002846:Chromatography, Affinity; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053645:Interleukin-2 Receptor alpha Subunit; D046911:Macromolecular Substances; D036961:Matrix Attachment Region Binding Proteins / Q000502:physiology*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
D002843:Chromatin; D006657:Histones; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D046911:Macromolecular Substances; D036961:Matrix Attachment Region Binding Proteins; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; C076189:SATB1 protein, human; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex