The proximal GC-rich region of p16INK4a gene promoter plays a role in its transcriptional regulation

Wang, Xiuli; Feng, Yunpeng; Pan, Lina; Wang, Yanle; Xu, Xin; Lü, Jun; Huang, Baiqu

doi:10.1007/s11010-007-9427-4

Cited by 27 publications

(12 citation statements)

References 31 publications

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“…Sp1 is a key regulator of p16 expression [188][189][190]. The proximal promoter of p16, a region essential for p16 expression, contains multiple Sp sites (Fig.…”

Section: P16mentioning

confidence: 99%

Sp1 and the ‘hallmarks of cancer’

2015

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For many years, transcription factor Sp1 was viewed as a basal transcription factor and relegated to a role in the regulation of so-called housekeeping genes. Identification of Sp1's role in recruiting the general transcription machinery in the absence of a TATA box increased its importance in gene regulation, particularly in light of recent estimates that the majority of mammalian genes lack a TATA box. In this review, we briefly consider the history of Sp1, the founding member of the Sp family of transcription factors. We review the evidence suggesting that Sp1 is highly regulated by post-translational modifications that positively and negatively affect the activity of Sp1 on a wide array of genes. Sp1 is over-expressed in many cancers and is associated with poor prognosis. Targeting Sp1 in cancer treatment has been suggested; however, our review of the literature on the role of Sp1 in the regulation of genes that contribute to the 'hallmarks of cancer' illustrates the extreme complexity of Sp1 functions. Sp1 both activates and suppresses the expression of a number of essential oncogenes and tumor suppressors, as well as genes involved in essential cellular functions, including proliferation, differentiation, the DNA damage response, apoptosis, senescence and angiogenesis. Sp1 is also implicated in inflammation and genomic instability, as well as epigenetic silencing. Given the apparently opposing effects of Sp1, a more complete understanding of the function of Sp1 in cancer is required to validate its potential as a therapeutic target.

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“…Sp1 is a key regulator of p16 expression [188][189][190]. The proximal promoter of p16, a region essential for p16 expression, contains multiple Sp sites (Fig.…”

Section: P16mentioning

confidence: 99%

Sp1 and the ‘hallmarks of cancer’

2015

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“…Methylation of the promoter of the 5′-CpG island in the p16 gene is one of the most common mechanisms of p16 inactivation in PDAC, emphasizing the importance of an epigenetic mechanism in modulating tumor suppressor function in this disease[12]. The result of this silencing is an interference of binding of permissive transcription factors, such as SP1, and the recruitment of MBDs that can recruit other proteins like HDACs and lead to chromatin compaction [33](fig. 2).…”

Section: Dna-based Epigeneticsmentioning

confidence: 99%

Insights into the epigenetic mechanisms controlling pancreatic carcinogenesis

McCleary‐Wheeler¹,

Lomberk²,

Weiss³

et al. 2013

Cancer Letters

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During the last couple decades, we have significantly advanced our understanding of mechanisms underlying the development of pancreatic ductural adenocarcinoma (PDAC). In the late 1990s into the early 2000s, a model of PDAC development and progression was developed as a multi-step process associated with the accumulation of somatic mutations. The correlation and association of these particular genetic aberrations with the establishment and progression of PDAC has revolutionized our understanding of this process. However, this model leaves out other molecular events involved in PDAC pathogenesis that contribute to its development and maintenance, specifically those being epigenetic events. Thus, a new model considering the new scientific paradigms of epigenetics will provide a more comprehensive and useful framework for understanding the pathophysiological mechanisms underlying this disease. Epigenetics is defined as the type of inheritance not based on a particular DNA sequence but rather traits that are passed to the next generation via DNA and histone modifications as well as microRNA-dependent mechanisms. Key tumor suppressors that are well established to play a role in PDAC may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. A noteworthy characteristic of epigenetic-based inheritance is its reversibility, which is in contrast to the stable nature of DNA sequence-based alterations. Given this nature of epigenetic alterations, it becomes imperative that our understanding of epigenetic-based events promoting and maintain PDAC continues to grow.

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“…Recently, it has been revealed that AT-rich consensus in the promoter region of the CpC2 and ERD1 genes may be critical for the responsiveness of the gene to dehydration or hormone ABA (Ditzer and Bartels, 2006;Tran et al, 2007). Wang et al (2007) have found that both the specific mutation of the proximal GC-rich (GC-box) region of p16 INK4a gene promoter and siRNA-induced transcription factor SP1 silencing resulted in the complete loss of its transcription regulation, indicating that GC-rich region of promoter is required for SP1 function, and plays a role in p16 INK4a gene transcription regulation. The studies by Fenoll et al (1990) showed that the upstream activating sequence (UAS) of the promoter from maize streak virus (MSV) contains a GC-rich element, which was responsible for the transcriptional activation and the binding of maize nuclear factors.…”

Section: Discussionmentioning

confidence: 99%

Isolation and analysis of a TIR-specific promoter from poplar

et al. 2007

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A 5′ flanking region of the well-conserved Toll/interleukin-1 receptor domain (TIR)-encoding sequence was isolated from the genomic DNA of Melampsora magnusiana Wagner resistant clones of hybrid triploid poplars [(Populus tomentosa × P. bolleana) × P. tomentosa]. Sequencing results and alignment analysis show that the obtained TIR-specific promoter (named as PtTIRp01) was 1,732 bp in length; moreover 3′ region of the PtTIRp01 contains a 398 bp complete TIR-encoding sequence, which significantly corresponds to the 5′ composition of TIR-NBS type gene PtDRG02, indicating that the obtained TIR-specific promoter region consists of 747 bp long 5′ region of TIR-NBS type gene PtDRG02 and its upstream region of promoter (985 bp). It was found that the 5′ region of TIR-NBS type gene PtDRG02 was characterized in the downstream region of the transcriptional start, named as 5′-untranslated region (5′ UTR), consisting of one 93 bp 5′-untranslation exon, one 213 bp intron and one 441 bp TIR-encoding open reading frame (ORF). In addition, several putative cis-acting motifs were present in the obtained TIR-specific promoter of PtDRG02, including one TATA box, one GC-rich, one AT-rich, one P-box, one 3-AF1 binding site, two CAAT boxes, two GT-1 motifs, three typical W-boxes, four I-boxes, and one multi-cis-acting fragment (MCF). The latter contains five types of regulatory elements (E4, G-box, ABRE motif, box1 and HVA1s), most of which were homologous to the cis-acting regulatory elements involved in the activation of defense genes in plants. Thus, it can be suggested that TIR-specific promoter might be a pathogen-inducible promoter and be necessary for the inducible expression of defense-related genes.

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The proximal GC-rich region of p16INK4a gene promoter plays a role in its transcriptional regulation

Cited by 27 publications

References 31 publications

Sp1 and the ‘hallmarks of cancer’

Sp1 and the ‘hallmarks of cancer’

Insights into the epigenetic mechanisms controlling pancreatic carcinogenesis

Isolation and analysis of a TIR-specific promoter from poplar

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