Faculty Collaboration Database

Histone release during transcription: acetylation stabilizes the interaction of the H2A-H2B dimer with the H3-H4 tetramer in nucleosomes that are on highly positively coiled DNA. Biochemistry 2005 Dec 13;44(49):16351-64

Date

12/08/2005

Pubmed ID

16331996

DOI

10.1021/bi050876o

Scopus ID

2-s2.0-28944442449 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

A high level of the post-translational modification, acetylation, is found on the N-terminal regions of the core histones H2A, H2B, H3, and H4 and is primarily located in the nucleosomes of active genes. An in vitro transcription system was applied, which utilizes T7 RNA polymerase and template DNAs that are either moderately or highly positively coiled, to determine whether acetylation alters the dynamics of histone displacement from these templates during transcription. To measure displacement, an excess of a competitor (negatively coiled DNA reconstituted with unlabeled H3-H4) was included during the transcription process. Acetylated but not unacetylated (3)H-labeled H3-H4 was found to displace with high frequency from the moderately positively coiled template. This displacement of acetylated H3-H4 was not observed when the template was highly positively coiled. Acetylated (3)H-labeled H2A-H2B also preferentially displaced to the competitor, but in this instance, transcription-induced stress on the highly positively coiled template was required. The histone chaperone, NAP1, was found to facilitate the displacement of both H3-H4 and H2A-H2B. Surprisingly, when acetylated H2A-H2B and acetylated H3-H4 were reconstituted together in the same nucleosomes, the displacement of acetylated H2A-H2B was much reduced during transcription. We conclude that acetylation alters nucleosome stability by enhancing displacement of H3-H4, while decreasing the displacement of H2A-H2B. These results are discussed with regard to potential in vivo conditions in which these observations may be relevant.

Author List

Wunsch A, Jackson V

Author

Vaughn E. Jackson PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylation
DNA
Dimerization
Histones
Nucleic Acid Conformation
Protein Binding
Protein Conformation
Transcription, Genetic