Data di Pubblicazione:
2018
Citazione:
An autoregulatory loop controls the expression of the transcription factor NF-Y / S. Belluti, V. Semeghini, V. Basile, G. Rigillo, V. Salsi, F. Genovese, D. Dolfini, C. Imbriano. - In: BIOCHIMICA ET BIOPHYSICA ACTA. GENE REGULATORY MECHANISMS. - ISSN 1874-9399. - 1861:5(2018 May), pp. 509-518.
Abstract:
The heterotrimeric NF-Y complex is a pioneer factor that binds to CCAAT-genes and regulates their transcription. NF-Y cooperates with multiple transcription factors and co-regulators in order to positively or negatively influence gene transcription. The recruitment of NF-Y to CCAAT box is significantly enriched in cancer-associated gene promoters loci and positively correlates with malignancy. NF-Y subunits, in particular the DNA-binding subunit NF-YA and the histone-fold subunit NF-YC, appear overexpressed in specific types of cancer. Here we demonstrate that NF-Y subunits expression is finely regulated through transcriptional and post-translational mechanisms thus allowing control over basal expression levels. NF-Y negatively regulates the transcription of the genes encoding for its subunits. DNA pull-down/affinity purification assay coupled with Mass Spectrometry identified putative co-regulators, such as Lamin A, involved in NF-YA gene transcription level. We also evidentiate how the stability of the complex is severely affected by the absence of one subunit. Our results identified for the first time one of the mechanisms responsible for NF-Y expression, which may be involved in the aberrant expression and activity observed in tumor cells and other pathological conditions.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
CCAAT box; gene regulation; NF-Y; transcription factor; CCAAT-Binding Factor; Gene Expression Regulation; HCT116 Cells; humans; Lamin Type A; mass spectrometry; neoplasms; promoter regions, genetic; protein binding; transcription, genetic; biophysics; structural biology; biochemistry; molecular biology; genetics
Elenco autori:
S. Belluti, V. Semeghini, V. Basile, G. Rigillo, V. Salsi, F. Genovese, D. Dolfini, C. Imbriano
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