The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2.
Sp1 and Sp3 are ubiquitously expressed mammalian transcription factors that function as activators or repressors. Although both transcription factors share a common domain involved in forming multimers, we demonstrate that Sp1 and Sp3 form separate complexes in estrogen-dependent human breast cancer cells. Sp1 and Sp3 complexes associate with histone deacetylases (HDACs) 1 and 2. Although most HDAC2 is not phosphorylated in the breast cancer cells, HDAC2 bound to Sp1 and Sp3 and cross-linked to chromatin in situ is highly enriched in a phosphorylated form that has a reduced mobility in SDS-polyacrylamide gels. We show that protein kinase CK2 is associated with and phosphorylates HDAC2. Alkaline phosphatase treatment of HDAC2 and Sp1 and Sp3 complexes reduced the associated HDAC activity. Protein kinase CK2 is up-regulated in several cancers including breast cancer, and Sp1 and Sp3 have key roles in estrogen-induced proliferation and gene expression in estrogen-dependent breast cancer cells. CK2 phosphorylation of HDAC2 recruited by Sp1 or Sp3 could regulate HDAC activity and alter the balance of histone deacetylase and histone acetyltransferase activities and dynamic chromatin remodeling of estrogen-regulated genes.
Sun
Jian-Min
JM
Manitoba Institute of Cell Biology, Winnipeg, Manitoba R3E 0V9, Canada.
Chen
Hou Yu
HY
Moniwa
Mariko
M
Litchfield
David W
DW
Seto
Edward
E
Davie
James R
JR
D000469:Alkaline Phosphatase / Q000378:metabolism; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism; D002455:Cell Division; D002843:Chromatin / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000737:chemistry*; D006801:Humans; D015151:Immunoblotting; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002843:Chromatin; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; D005557:Formaldehyde; D005982:Glutathione Transferase; D000469:Alkaline Phosphatase; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D002945:Cisplatin