Beschreibung:
Transcription-associated chromatin modifications are recognized now as important regulators of gene expression. One of them, the monoubiquitination of lysine 120 of histone H2B (H2Bub1), is associated with actively transcribed genes. It was shown to change the physical properties of the chromatin as well as serve as a recognition mark for regulatory chromatin-binding proteins. The misregulation of H2Bub1-modifying machinery has been observed to be tightly linked with different types of cancer. Many aspects of regulation of H2B monoubiquitination remain unknown. In the course of this study we presented the data which links H2Bub1 to the modifications of RNA polymerase II, proving that H2Bub1 does not depend on transcription per se. We also clarified aspects of the regulation of the H2B ubiquitinating enzymes. A separate interesting question investigated in this study is a rapid and massive loss of H2Bub1 following various cell stresses. Preliminary mechanism and signaling pathways which control this process were discovered. Together, these studies have uncovered important mechanisms controlling H2Bub1 and may serve as a basis for developing more potent strategies to combat cancer.