MinireviewHistone acetylation and chromatin remodeling: which comes first?
Introduction
The packaging of DNA into chromatin prevents access of the transcription machinery necessary to regulate gene expression. To overcome this repressive barrier, the cell contains numerous, multi-subunit chromatin-remodeling enzymes, which work to loosen and open up chromatin structure. The SWI/SNF complex is a multi-subunit, ATP-dependent chromatin-remodeling machine. It is able to use the energy of ATP hydrolysis to alter histone–DNA contacts, and in many cases, leads to movement of the histone octamer along DNA or to transfer of the octamer to another chromosome (for reviews, see [1], [2]). The SAGA complex represents a second class of chromatin-remodeling complexes, histone acetyltransferases (HATs), which covalently modify the amino terminal tails of the histone proteins, possibly leading to alteration of histone–DNA or histone–histone interactions. The multi-subunit SAGA complex contains the yeast Gcn5 protein that possesses its catalytic activity, and has many components that were previously described as being involved in transcription regulation, including Ada, Spt, and Taf proteins (for review, see [3]).
Section snippets
Evidence for functional interplay between SWI/SNF and SAGA
Over the last few years, evidence for a functional interaction between SWI/SNF and HAT complexes, and in particular the SAGA complex, has accumulated. Many inducible genes whose expression is dependent on the yeast SWI/SNF complex also have been found to be dependent on Gcn5. These genes include INO1, HO, SUC2, HIS3, and Ty elements [4], [5], [6], [7], [8]. Moreover, GCN5 and genes encoding SWI/SNF components exhibit similar genetic interactions with chromatin components. Mutations in the SIN1
Histone acetylation precedes chromatin remodeling
A recent study in support of acetylation before remodeling indicated that acetylation acts as a signal for ATP-dependent remodeling complexes at the PHO8 promoter [24]. Using in vivo chromatin immunoprecipitation, it was shown that when chromatin remodeling was blocked at the PHO8 promoter by inactivation or deletion of Swi2/Snf2, there was a peak of hyperacetylation (both H3 and H4) at the promoter. If remodeling was allowed to go to completion (i.e., in a wild-type yeast strain), the
Chromatin remodeling precedes histone acetylation
It is possible that ATP-dependent remodeling occurs prior to acetylation at some promoters. Some recent studies have found that this seems to be the case at the yeast HO promoter [30], [31]. Furthermore, many genes that are expressed in mitosis were shown to require remodeling before recruitment of HAT activity and efficient expression of the genes [15]. In studies of the HO promoter, in vivo chromatin immunoprecipitation assays demonstrated that the binding of the Swi5 activator to its site in
Conclusions
It seems likely that the recruitment and action of SWI/SNF and HAT complexes at promoters will turn out to be promoter specific, possibly depending on when the gene is most highly expressed during the cell division cycle. Future studies that focus on other genes that are both SWI/SNF-dependent and HAT-dependent will give us a better understanding of the interplay between these chromatin-modifying complexes at target promoters.
Acknowledgments
The work was supported by NIGMS Grant R37 GM47867 to J.L.W. J.L.W. is an Associate Investigator of the Howard Hughes Medical Institute.
References (32)
- et al.
Activation of the yeast HO gene by release from multiple negative controls
Cell
(1987) - et al.
Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays
Mol. Cell
(1999) - et al.
Transcriptional activation by Gcn4p involves independent interactions with the SWI/SNF complex and the SRB/Mediator
Mol. Cell
(1999) - et al.
Global role for chromatin remodeling enzymes in mitotic gene expression
Cell
(2000) - et al.
Histone acetyltransferase complexes stabilize SWI/SNF binding to promoter nucleosomes
Cell
(2001) - et al.
A transient histone hyperacetylation signal marks nucleosomes for remodeling at the PHO8 promoter in vivo
Mol. Cell
(2001) - et al.
Ordered recruitment of chromatin modifying and general transcription factors to the IFN-β promoter
Cell
(2000) - et al.
ATP-driven chromatin remodeling activity and histone acetyltransferases act sequentially during transcription by RAR/RXR in vitro
Mol. Cell
(2000) - et al.
ATP-dependent nucleosome remodeling and histone hyperacetylation synergistically facilitate transcription of chromatin
J. Biol. Chem.
(2001) - et al.
Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter
Cell
(1999)
ATP-dependent chromatin remodeling complexes
Mol. Cell. Biol.
ATP-dependent remodeling and acetylation as regulators of chromatin fluidity
Genes Dev.
Histone acetyltransferases
Annu. Rev. Biochem.
Continuous and widespread roles for the SWI–SNF complex in transcription
EMBO J.
Role for ADA/GCN5 products in antagonizing chromatin-mediated transcriptional repression
Mol. Cell. Biol.
Essential functional interactions of SAGA, a Saccharomyces cerevisiae complex of Spt Ada and Gcn5 proteins with the Snf/Swi and Srb/mediator complexes
Genetics
Cited by (0)
- 1
Present address: Department of Cell Biology and Physiology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.