Cell-line specific chromatin acetylation at the Sox10-Pax3 enhancer site modulates the RET proto-oncogene expression.
The RET gene is expressed with high tissue and stage specificity during development. Understanding its transcriptional regulation might provide new clues to clarify developmental mechanisms. Here we show that the histone deacetylase inhibitor sodium butyrate (NaB) increases RET transcription in cells displaying low levels of its mRNA, while it has no effect in cells expressing at high levels. Chromatin immunoprecipitation (ChIP) experiments showed increased histone acetylation within the 5' flanking [corrected] region, in particular the Sox10-Pax3 enhancer site, due to NaB. Accordingly, ChIP showed different acetylation levels at the Sox10-Pax3 site associated with cell-line specific RET transcription rates. Concluding, chromatin acetylation targeted to functional sequences in the RET regulatory region may control its transcription.
Laboratory of Molecular Genetics, G. Gaslini Institute, Largo G. Gaslini 5, 16148, Genova, Italy.
Francesca
F
Puppo
Paola
P
Griseri
Mirco
M
Fanelli
Francesca
F
Schena
Giovanni
G
Romeo
PierGiuseppe
P
Pelicci
Isabella
I
Ceccherini
Roberto
R
Ravazzolo
Giovanna
G
Patrone
D000107:Acetylation; D001665:Binding Sites; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects
D002087:Butyrates; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D006609:High Mobility Group Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C000715470:MAS1 protein, human; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila