期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：32
页码：13546-13551
DOI：10.1073/pnas.0902233106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Histone H1 and high-mobility group A (HMGA) proteins compete dynamically to modulate chromatin structure and regulate DNA transactions in eukaryotes. In prokaryotes, HMGA-like domains are known only in Myxococcus xanthus CarD and its Stigmatella aurantiaca ortholog. These have an N-terminal module absent in HMGA that interacts with CarG (a zinc-associated factor that does not bind DNA) to form a stable complex essential in regulating multicellular development, light-induced carotenogenesis, and other cellular processes. An analogous pair, CarDAd and CarGAd, exists in another myxobacterium, Anaeromyxobacter dehalogenans. Intriguingly, the CarDAd C terminus lacks the hallmark HMGA DNA-binding AT-hooks and instead resembles the C-terminal region (CTR) of histone H1. We find that CarDAd alone could not replace CarD in M. xanthus. By contrast, when introduced with CarGAd, CarDAd functionally replaced CarD in regulating not just 1 but 3 distinct processes in M. xanthus, despite the lower DNA-binding affinity of CarDAd versus CarD in vitro. The ability of the cognate CarDAd-CarGAd pair to interact, but not the noncognate CarDAd-CarG, rationalizes these data. Thus, in chimeras that conserve CarD-CarG interactions, the H1-like CTR of CarDAd could replace the CarD HMGA AT-hooks with no loss of function in vivo. More tellingly, even chimeras with the CarD AT-hook region substituted by human histone H1 CTR or full-length H1 functioned in M. xanthus. Our domain-swap analyses showing functional equivalence of HMGA AT-hooks and H1 CTR in prokaryotic transcriptional regulation provide molecular insights into possible modes of action underlying their biological roles.
