title: A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells.
abstract: The Sox6 transcription factor plays critical roles in various cell types, including erythroid cells. Sox6-deficient mice are anemic due to impaired red cell maturation and show inappropriate globin gene expression in definitive erythrocytes. To identify new Sox6 target genes in erythroid cells, we used the known repressive double Sox6 consensus within the εy-globin promoter to perform a bioinformatic genome-wide search for similar, evolutionarily conserved motifs located within genes whose expression changes during erythropoiesis. We found a highly conserved Sox6 consensus within the Sox6 human gene promoter itself. This sequence is bound by Sox6 in vitro and in vivo, and mediates transcriptional repression in transient transfections in human erythroleukemic K562 cells and in primary erythroblasts. The binding of a lentiviral transduced Sox6FLAG protein to the endogenous Sox6 promoter is accompanied, in erythroid cells, by strong downregulation of the endogenous Sox6 transcript and by decreased in vivo chromatin accessibility of this region to the PstI restriction enzyme. These observations suggest that the negative Sox6 autoregulation, mediated by the double Sox6 binding site within its own promoter, may be relevant to control the Sox6 transcriptional downregulation that we observe in human erythroid cultures and in mouse bone marrow cells in late erythroid maturation.
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy. mcclaudio061281@gmail.com
authors.forename: Claudio
authors.initials: C
authors.lastname: Cantu'
authors.forename: Vito
authors.initials: V
authors.lastname: Grande
authors.forename: Ilaria
authors.initials: I
authors.lastname: Alborelli
authors.forename: Letizia
authors.initials: L
authors.lastname: Cassinelli
authors.forename: Ileana
authors.initials: I
authors.lastname: Cantu'
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Colzani
authors.forename: Rossella
authors.initials: R
authors.lastname: Ierardi
authors.forename: Luisa
authors.initials: L
authors.lastname: Ronzoni
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Giuliana
authors.initials: G
authors.lastname: Ferrari
authors.forename: Sergio
authors.initials: S
authors.lastname: Ottolenghi
authors.forename: Antonella
authors.initials: A
authors.lastname: Ronchi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D017124:Conserved Sequence; D015536:Down-Regulation / Q000235:genetics*; D041905:Erythroid Cells / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D011401:Promoter Regions, Genetic; D055755:SOXD Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C486270:SOX6 protein, human; D055755:SOXD Transcription Factors; C095939:Sox6 protein, mouse