Sumoylation of ING2 regulates the transcription mediated by Sin3A

Abstract

ING2 (inhibitor of growth 2) is a candidate tumorsuppressor 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.

ING2 controls the G1to S-phase transition by regulating p21 expression

“…[16][17][18] The recruitment of mSin3a/HDAC1 by ING2 to H3K4Me3 has been associated with both gene repression 15 and gene activation. 19 Recently, we identified that ING2 can be sumoylated and that this post-translational modification is important for the binding of ING2 with mSin3a. Moreover, ING2 sumoylation is required for the binding of the complex mSin3a/ING2 to a subset of gene promoters to regulate their transcription.…”

“…Moreover, ING2 sumoylation is required for the binding of the complex mSin3a/ING2 to a subset of gene promoters to regulate their transcription. 19 Our aim is to better understand the role played by ING2 under "physiological" conditions without additional exogenous stress. Recently, we have shown that downregulation of ING2, as observed in tumors causes defects in replication forks' progression, leading to genome instability.…”

SIN3A, Generally Regarded as a Transcriptional Repressor, Is Required for Induction of Gene Transcription by the Aryl Hydrocarbon Receptor

“…Although generally associated with repression, HDAC activity characteristic of the SIN3A-HDAC complex has been known to alter chromatin domains that can activate gene transcription (27), and several studies have demonstrated that SIN3A is required for the expression of particular genes (9, 13, 28 -34). In some of these cases, SIN3A has been shown to bind the gene in question (29,(31)(32)(33)(34). Our studies now demonstrate that rapid recruitment of SIN3A to the corresponding enhancer and proximal promoter regions occurs after transcriptional activation of a highly inducible gene (CYP1A1).…”

Decreased expression of ING2 gene and its clinicopathological significance in Chinese NSCLC patients

“…Other studies provided further evidence that ING2 was involved in tumorigenesis. Two studies by Okano [27] and Ythier D [28] described the reduced expression of ING2 in lung cancer cell lines and NSCLC respectively. In another study by Lu F [29], a reduced nuclear expression of ING2 was observed in human melanomas when compared to dysplastic nevi, while no correlation between ING2 nuclear expression and tumor growth phase or tumor stage was established.…”