溴结构域在将染色质修饰复合物锚定到启动子核小体中的功能与选择性

Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes.

作者信息

Hassan Ahmed H, Prochasson Philippe, Neely Kristen E, Galasinski Scott C, Chandy Mark, Carrozza Michael J, Workman Jerry L

机构信息

Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 306 Althouse Laboratory, University Park, PA 16802, USA.

出版信息

Cell. 2002 Nov 1;111(3):369-79. doi: 10.1016/s0092-8674(02)01005-x.

DOI:10.1016/s0092-8674(02)01005-x

PMID:12419247

Abstract

The functions of the SAGA and SWI/SNF complexes are interrelated and can form stable "epigenetic marks" on promoters in vivo. Here we show that stable promoter occupancy by SWI/SNF and SAGA in the absence of transcription activators requires the bromodomains of the Swi2/Snf2 and Gcn5 subunits, respectively, and nucleosome acetylation. This acetylation can be brought about by either the SAGA or NuA4 HAT complexes. The bromodomain in the Spt7 subunit of SAGA is dispensable for this activity but will anchor SAGA if it is swapped into Gcn5, indicating that specificity of bromodomain function is determined in part by the subunit it occupies. Thus, bromodomains within the catalytic subunits of SAGA and SWI/SNF anchor these complexes to acetylated promoter nucleosomes.

摘要

SAGA和SWI/SNF复合物的功能相互关联，且在体内能够在启动子上形成稳定的“表观遗传标记”。我们在此表明，在缺乏转录激活因子的情况下，SWI/SNF和SAGA在启动子上的稳定占据分别需要Swi2/Snf2和Gcn5亚基的溴结构域以及核小体乙酰化。这种乙酰化可由SAGA或NuA4 HAT复合物实现。SAGA的Spt7亚基中的溴结构域对于此活性并非必需，但如果将其替换到Gcn5中则会锚定SAGA，这表明溴结构域功能的特异性部分由其所在的亚基决定。因此，SAGA和SWI/SNF催化亚基内的溴结构域将这些复合物锚定到乙酰化的启动子核小体上。