Post-translational modifications in activation and inhibition of Oct-1-DNA binding complex in H2B and other diverse gene regulation: Prediction of interplay sites

摘要

Octamer DNA binding transcription factors play important roles in housekeeping and specific gene regulations. Octamer DNA binding transcription factor-1 (Oct-1), expressed ubiquitously, is a multifunctional molecule. The binding sites of Oct-1 are the promoters of H2B gene and the genes of snRNA, U2, U6, and 7SK, yet Oct-1 has been described as constitutively expressed transcription factor regulating the expression of housekeeping genes. Diverse tissue-specific genes regulations by Oct-1 include genes for interleukins (IL) 2, 3, 5; the granulocyte-macrophagal colony-stimulating factor, immunoglobulins α, β, Ly9; the endocrine-associated Pit-1 gene; the genes for gonadoliberin, prolactin, the thyroid transcription factor, and thyrotropin. The most interesting aspect of the gene regulations of Oct-1 includes both activation and inhibition of transcription. These opposite regulations of Oct-1 have been described through presence/absence of a post-translational modification (PTM) in its different domains. We propose a mechanism of interplay of different PTMs or presence/absence of PTMs in the different domains of Oct-1. We also suggest that the absence of phosphorylation and acetylation in G1 and S phases of the cell cycle is associated with interplay of methylation and O-GlcNAc modification. This interplay of O-GlcNAc modification with the phosphorylation and methylation with acetylation in POU sub-domain of Oct-1 may facilitate the formation of Oct-1-DNA complex, consequently activating H2B gene transcription. Whereas, in G2 and M phases these sites are occupied by phosphate resulting in inhibition of Oct-1-DNA complex formation leading to the suppression of H2B gene transcription.