Trans-tail regulation-mediated suppression of cryptic transcription

Crosstalk between post-translational modifications of histone proteins influences the regulation of chromatin structure and gene expression. Among such crosstalk pathways, the best-characterized example is H2B monoubiquitination-mediated H3K4 and H3K79 methylation, which is referred to as trans-tail regulation. Although many studies have investigated the fragmentary effects of this pathway on silencing and transcription, its ultimate contribution to transcriptional control has remained unclear. Recent advances in molecular techniques and genomics have, however, revealed that the trans-tail crosstalk is linked to a more diverse cascade of histone modifications and has various functions in cotranscriptional processes. Furthermore, H2B monoubiquitination sequentially facilitates H3K4 dimethylation and histone sumoylation, thereby providing a binding platform for recruiting Set3 complex proteins, including two histone deacetylases, to restrict cryptic transcription from gene bodies. The removal of both ubiquitin and SUMO, small ubiquitin-like modifier, modifications from histones also facilitates a change in the phosphorylation pattern of the RNA polymerase II C-terminal domain that is required for subsequent transcriptional elongation. Therefore, this review describes recent findings regarding trans-tail regulation-driven processes to elaborate on their contribution to maintaining transcriptional fidelity.