A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells

Claudio Cantu', Vito Grande, Ilaria Alborelli, Letizia Cassinelli, Ileana Cantu', Maria Teresa Colzani, Rossella Ierardi, Luisa Ronzoni, Maria Domenica Cappellini, Giuliana Ferrari, Sergio Ottolenghi, Antonella Ronchi

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)486-501
Number of pages16
JournalNucleic Acids Research
Volume39
Issue number2
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Erythroid Cells
Down-Regulation
Globins
Binding Sites
Genes
Gene Expression
Erythroblasts
K562 Cells
Erythropoiesis
Computational Biology
Bone Marrow Cells
Chromatin
Transfection
Homeostasis
Transcription Factors
Erythrocytes
Genome
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Cantu', C., Grande, V., Alborelli, I., Cassinelli, L., Cantu', I., Colzani, M. T., ... Ronchi, A. (2011). A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells. Nucleic Acids Research, 39(2), 486-501. https://doi.org/10.1093/nar/gkq819

A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells. / Cantu', Claudio; Grande, Vito; Alborelli, Ilaria; Cassinelli, Letizia; Cantu', Ileana; Colzani, Maria Teresa; Ierardi, Rossella; Ronzoni, Luisa; Cappellini, Maria Domenica; Ferrari, Giuliana; Ottolenghi, Sergio; Ronchi, Antonella.

In: Nucleic Acids Research, Vol. 39, No. 2, 01.2011, p. 486-501.

Research output: Contribution to journalArticle

Cantu', C, Grande, V, Alborelli, I, Cassinelli, L, Cantu', I, Colzani, MT, Ierardi, R, Ronzoni, L, Cappellini, MD, Ferrari, G, Ottolenghi, S & Ronchi, A 2011, 'A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells', Nucleic Acids Research, vol. 39, no. 2, pp. 486-501. https://doi.org/10.1093/nar/gkq819
Cantu' C, Grande V, Alborelli I, Cassinelli L, Cantu' I, Colzani MT et al. A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells. Nucleic Acids Research. 2011 Jan;39(2):486-501. https://doi.org/10.1093/nar/gkq819
Cantu', Claudio ; Grande, Vito ; Alborelli, Ilaria ; Cassinelli, Letizia ; Cantu', Ileana ; Colzani, Maria Teresa ; Ierardi, Rossella ; Ronzoni, Luisa ; Cappellini, Maria Domenica ; Ferrari, Giuliana ; Ottolenghi, Sergio ; Ronchi, Antonella. / A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells. In: Nucleic Acids Research. 2011 ; Vol. 39, No. 2. pp. 486-501.
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