Sumoylation of ING2 regulates the transcription mediated by Sin3A.
ING2 (inhibitor of growth 2) is a candidate tumor-suppressor gene involved in cell cycle control, apoptosis and senescence. Although the functions of ING2 within the chromatin remodeling complex Sin3A/histone deacetylase (HDAC) and in the p53 pathway have been described, how ING2 itself is regulated remains unknown. In this study we report for the first time that ING2 can be sumoylated by small ubiquitin-like modifier 1 (SUMO1) on lysine 195 both in vitro and in vivo. Strikingly, ING2 sumoylation enhances its association with Sin3a. We provide evidences that ING2 can bind to the promoter of genes to mediate their expression and that sumoylation of ING2 is required for this binding to some of these genes. Among them, we identified the gene TMEM71 (transmembrane protein 71), whose expression is regulated by ING2 sumoylation. ING2 must be sumoylated to bind to the promoter of TMEM71 and to recruit the Sin3A chromatin-modifying complex to this promoter, in order to regulate TMEM71 transcription. Hence, sumoylation of ING2 enhances its binding to the Sin3A/HDAC complex and is required to regulate gene transcriptions.
Ythier
D
D
Molecular Bases of Lung Cancer Progression, INSERM U823, Institut Albert Bonniot, Université Joseph Fourier, Grenoble, France.
Larrieu
D
D
Binet
R
R
Binda
O
O
Brambilla
C
C
Gazzeri
S
S
Pedeux
R
R
D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D013347:Subcellular Fractions / Q000378:metabolism; D058207:Sumoylation; D014158:Transcription, Genetic / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D017931:DNA Primers; D018398:Homeodomain Proteins; C444654:ING2 protein, human; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D025521:Tumor Suppressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex