• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Functional dissection of the NuA4 histone acetyltransferase reveals its role as a genetic hub and that Eaf1 is essential for complex integrity.

The Saccharomyces cerevisiae NuA4 histone acetyltransferase complex catalyzes the acetylation of histone H4 and the histone variant Htz1 to regulate key cellular events, including transcription, DNA repair, and faithful chromosome segregation. To further investigate the cellular processes impacted by NuA4, we exploited the nonessential subunits of the complex to build an extensive NuA4 genetic-interaction network map. The map reveals that NuA4 is a genetic hub whose function buffers a diverse range of cellular processes, many not previously linked to the complex, including Golgi complex-to-vacuole vesicle-mediated transport. Further, we probe the role that nonessential subunits play in NuA4 complex integrity. We find that most nonessential subunits have little impact on NuA4 complex integrity and display between 12 and 42 genetic interactions. In contrast, the deletion of EAF1 causes the collapse of the NuA4 complex and displays 148 genetic interactions. Our study indicates that Eaf1 plays a crucial function in NuA4 complex integrity. Further, we determine that Eaf5 and Eaf7 form a subcomplex, which reflects their similar genetic interaction profiles and phenotypes. Our integrative study demonstrates that genetic interaction maps are valuable in dissecting complex structure and provides insight into why the human NuA4 complex, Tip60, has been associated with a diverse range of pathologies.

Pubmed ID: 18212056

Authors

  • Mitchell L
  • Lambert JP
  • Gerdes M
  • Al-Madhoun AS
  • Skerjanc IS
  • Figeys D
  • Baetz K

Journal

Molecular and cellular biology

Publication Data

April 10, 2008

Associated Grants

None

Mesh Terms

  • Acetylation
  • Acetyltransferases
  • Amino Acid Sequence
  • DNA-Binding Proteins
  • Gene Expression Regulation, Fungal
  • Golgi Apparatus
  • Histone Acetyltransferases
  • Histones
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational
  • Protein Transport
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Structure-Activity Relationship
  • Transcription Factors
  • Transcription, Genetic
  • Transport Vesicles
  • Vacuoles