H2B ubiquitylation in transcriptional control: a FACT-finding mission
- Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
This extract was created in the absence of an abstract.
A little more than 10 years ago, the laboratory of David Allis published two pioneering papers in Cell (Brownell et al. 1996; Mizzen et al. 1996) demonstrating that the transcriptional coactivators Gcn5 and TAFII250 (TAF1) could acetylate histones as part of their transcriptional activating functions. These studies fundamentally altered our understanding of transcriptional regulation and heralded a new era of research that has focused on understanding how covalent histone modifications regulate gene transcription. A recent flurry of studies has linked one modification in particular, histone H2B monoubiquitylation (H2Bub1), to the regulation of the elongation phase of the gene transcription cycle. A study in this issue of Genes & Development from the Allis laboratory (Tanny et al. 2007) further strengthens this connection by showing that H2Bub1 functions in vivo to promote efficient RNA polymerase II (Pol II) elongation through chromatin. We will discuss the work up to this point that establishes H2Bub1 as a modification linked to transcriptional regulation, highlighting the importance of this current study, along with others, in shaping our understanding of how H2Bub1 promotes transcription elongation through a chromatin landscape.
A little goes a long way—H2B ubiquitylation as a ‘trans’ient modification
Protein ubiquitylation occurs through an enzymatic cascade involving three different factors plus ubiquitin. Initially, a ubiquitin activating enzyme (E1) creates an E1–ubiquitin intermediate through the formation of a thioester bond in an ATP-dependent reaction (Pickart 2001). This activated form of ubiquitin is then transferred to a ubiquitin-conjugating (E2) enzyme that, in partnership with an E3 ubiquitin ligase, will mediate ubiquitin transfer to selective lysine residues on substrate proteins. Typically, polyubiquitylation signals a protein to be degraded via the 26S proteasome, whereas monoubiquitylation modifies protein function (Pickart 2001). H2Bub1 occurs at the Lys 123 position in budding yeast (Saccharomyces cerevisiae) and at the Lys 120 position (K120) in humans (Zhang 2003; Osley 2004). Although histones …
