Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo.
SATB1 regulates gene expression by acting as a "docking site" for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters. However, how these contrasting effectors act at the level of SATB1 is not clear. We show here that phosphorylation by PKC acts as a switch to determine whether SATB1 interacts with HDAC1 or PCAF. Phosphorylation and dephosphorylation of SATB1 exerted opposing effects on MAR-linked reporter activity in vivo. SATB1 interacted with both CBP/p300 and PCAF HATs; however, these interactions resulted in the acetylation of the PDZ-like domain of SATB1 by PCAF but not by CBP/p300 and resulted in loss of its DNA binding activity. Using the T cell activation model, we provide mechanistic insights into how IL-2 transcription is reciprocally governed by the phosphorylation status of SATB1 and propose that a similar mechanism may dictate the ability of SATB1 to function as a global regulator.
Pavan Kumar
P
P
National Centre for Cell Science, Ganeshkhind, Pune 411007, India.
Purbey
Prabhat Kumar
PK
Sinha
Chandan Kumar
CK
Notani
Dimple
D
Limaye
Amita
A
Jayani
Ranveer S
RS
Galande
Sanjeev
S
D000107:Acetylation; D001665:Binding Sites; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D002846:Chromatography, Affinity; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D017930:Genes, Reporter; D051548:Histone Acetyltransferases / Q000378:metabolism; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015151:Immunoblotting; D019169:Jurkat Cells; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D036961:Matrix Attachment Region Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D009281:Naphthalenes / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D051548:Histone Acetyltransferases; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D008156:Luciferases; D036961:Matrix Attachment Region Binding Proteins; D009281:Naphthalenes; D011493:Protein Kinase C; D011994:Recombinant Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C076189:SATB1 protein, human; C061465:calphostin complex; C012589:trichostatin A; C110550:HDAC1 protein, human