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Commentary
Histone modifications: Now summoning sumoylation
Gene Expression and Regulation Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104
Sumoylation may be the signal that initiates attenuation followed by gene repression.
Histones can be modified in many ways to affect gene expression, including acetylation/deacetylation (1), phosphorylation (2), methylation (3), and ubiquitylation (4). Now, in this issue of PNAS, Shiio and Eisenman (5) report that sumoylation is yet another histone modification, and, interestingly, it may regulate transcriptional repression. Although there may appear to be a bewildering array of histone modifications involved with gene regulation, there could be a fairly simple paradigm underlying them.
Eukaryotic DNA is packaged within the nucleus through its association with histone proteins (H2A, H2B, H3, and H4), forming the fundamental repeating unit of chromatin, the nucleosome. The precise architecture of chromatin dictates whether it is permissive or resistant to transcription and other DNA-templated processes, such as replication, DNA repair, and recombination. Hence, it is not surprising that mechanisms that promote changes in chromatin structure are central to transcriptional regulation. One key pathway to alter chromatin structure involves covalent modifications of the histone tails.
Small ubiquitin-related modifier (SUMO) shares 18% identity with ubiquitin and adopts a similar 3D structure (6). Ubiquitylation has a role in protein degradation, whereas SUMO does not. The size of SUMO and ubiquitin (11 and 9 kDa, respectively) clearly distinguishes them from the other known posttranslation modifications of histones, which are all small chemical groups. SUMO and its ATP-dependent pathway of conjugation to substrates are con served in all eukaryotes investigated, yeast through humans.
One important consideration regarding sumoylation of histones is that its target residue, lysine, is a putative substrate for multiple modifying enzymes (Table 1). Acetylation of lysines is dynamically opposed by deacetylating enzymes. Typically, histone acetylation is activating and histone deacetylation is repressing, and, in a symmetrical fashion, DNA-bound activators and repressors recruit these enzymes to target genes
* To whom correspondence should be addressed. E-mail: berger@wistar.upenn.edu.
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