Edited by Wilhelm JustKeywords: H2B Monoubiquitination Chromatin Tumor suppressor Cancer Epigenetic a b s t r a c tThe post-translational modification of histone proteins plays an important role in controlling cell fate by directing essentially all DNA-associated nuclear processes. Misregulation and mutation of histone modifying enzymes is a hallmark of tumorigenesis. However, how these different epigenetic modifications lead to tumor initiation and/or progression remains poorly understood. Recent studies have uncovered a potential tumor suppressor role for histone H2B monoubiquitination (H2Bub1). Like many other histone modifications, H2Bub1 has diverse functions and plays roles both in transcriptional activation and repression as well as in controlling mRNA processing and directing DNA repair processes. Notably, H2Bub1 has been linked to transcriptional elongation and is preferentially found in the transcribed region of active genes. Its activity is intimately connected to active transcription and the transcriptional elongation regulatory protein cyclindependent kinase-9 (CDK9) and the facilitates chromatin transcription (FACT) complex. This review provides an overview of the current understanding of H2Bub1 function in mammalian systems with a particular emphasis on its role in cancer and potential options for exploiting this knowledge for the treatment of cancer.Ó 2012 Federation of European Biochemical Societies. Published by Elsevier B.V.
Histone modificationsEpigenetic modifications are essential in controlling DNA associated processes such as cell type-specific gene expression, DNA replication and DNA repair. While much focus has been placed on DNA methylation, post-translational modifications of core histones also play an essential, but only poorly understood role in these processes. Chromatin is the composite of packaged nuclear DNA with its associated proteins. The basic unit of chromatin is the nucleosome containing approximately 147 bp of DNA wrapped around an octamer containing two each of histones H2A, H2B, H3 and H4. Histone octamers are then packaged into higher order chromatin structures by the interactions between individual nucleosomes and the binding of other proteins such as the linker histone H1, heterochromatin protein 1 (HP1), etc. Each of the core histones can be modified by a number of post-translational modifications such as the methylation of arginine and lysine residues, acetylation of lysine residues and phosphorylation of serine or threonine residues. Modifications of the core histones have been hypothesized to make up a ''histone code'' which controls DNAassociated processes in different ways according to the repertoire of modifications present at a given chromatin region [1,2]. Furthermore, a number of other post-translational modifications of histones such as formylation [3,4], sumoylation [5], crotonylation[6], ADP-ribosylation [7], etc., have been identified, but their functions remain mostly enigmatic.In addition to the more common modifications like methylation, acetylation ...