Nhp6: a small but powerful effector of chromatin structure in Saccharomyces cerevisiae

Abstract

The small Nhp6 protein from budding yeast is an abundant protein that binds DNA non-specifically and bends DNA sharply. It contains only a single HMGB domain that binds DNA in the minor groove and a basic N-terminal extension that wraps around DNA to contact the major groove. This review describes the genetic and biochemical experiments that indicate Nhp6 functions in promoting RNA pol III transcription, in formation of preinitiation complexes at promoters transcribed by RNA pol II, and in facilitating the activity of chromatin modifying complexes. The FACT complex may provide a paradigm for how Nhp6 functions with chromatin factors, as Nhp6 allows Spt16-Pob3 to bind to and reorganize nucleosomes in vitro.

Fig 1

Model for how Swi/Snf, Gcn5 and Nhp6 all contribute to formation of the TBP-TFIIB-TFIIA-DNA complex. Swi/Snf, Gcn5 and Nhp6 all function in the same process. A single mutation affecting Swi/Snf, Gcn5 or Nhp6 is tolerated, but mutations affecting more than one pathway results in synthetic lethality. Similarly, certain mutations in TBP or TFIIA that modestly affect complex formation can be tolerated, but these mutations are lethal in when Swi/Snf, Gcn5 or Nhp6 are also mutated.

Fig 2

Two step model for nucleosome reorganization by FACT. In the first step a molar excess of Nhp6 is required to effect changes in nucleosome structure. This subtly altered nucleosome can then be recognized by Spt16-Pob3, and FACT then makes more substantial changes in nucleosome structure.