Roles of histone acetyltransferases and deacetylases in gene regulation

  title={Roles of histone acetyltransferases and deacetylases in gene regulation},
  author={Min-Hao Kuo and C. David Allis},
Acetylation of internal lysine residues of core histone N‐terminal domains has been found correlatively associated with transcriptional activation in eukaryotes for more than three decades. Recent discoveries showing that several transcriptional regulators possess intrinsic histone acetyltransferase (HAT) and deacetylase (HDAC) activities strongly suggest that histone acetylation and deacetylation each plays a causative role in regulating transcription. Intriguingly, several HATs have been… 

Structure and function of histone acetyltransferases

  • R. Marmorstein
  • Biology, Chemistry
    Cellular and Molecular Life Sciences CMLS
  • 2001
Structurally variable N- and C-terminal domains appear to contain a related scaffold that mediates histone substrate binding and provide a framework for understanding the structure and function of other more divergent HAT proteins such as TAFII250 and CBP/p300.

Histone Deacetylases as Transcriptional Activators? Role Reversal in Inducible Gene Regulation

A number of exceptions are described, indicating a previously unrecognized dynamic complexity in gene regulation by reversible acetylation in eukaryotic gene expression.

Acetylation and chromosomal functions.

Histone acetylation and histone deacetylation

Methods for measuring the histone acetyltransferase (HAT) and deacetylase (HDAC) activity of A549 cells are described and a technique for examining HAT activity associated with a specific co-activator CBP isolated by immunoprecipitation is described.

Dynamic histone acetylation and its involvement in transcription Review Article

To fully appreciate the role of acetylation in transcription, the dynamic nature of this event must be understood.

Untargeted tail acetylation of histones in chromatin: lessons from yeast.

The current understanding of the mechanisms by which untargeted KAT and HDAC activities modulate the acetylation state of nucleosomal histones is reviewed, focusing on results obtained for H3 and H4 in budding yeast.

Cloning and Characterization of a Novel Human Class I Histone Deacetylase That Functions as a Transcription Repressor*

Results indicate that HDAC8 is a novel member of the histone deacetylase family, which may play a role in the development of a broad range of tissues and potentially in the etiology of cancer.

Structure of histone acetyltransferases.

A comparison of structure determination of the divergent HAT enzymes Hat1, Gcn5/PCAF and Esa1 reveals a structurally conserved central core domain that mediates extensive interactions with the acetyl-coenzyme A cofactor, and structurally divergent N and C-terminal domains.



ESA1 is a histone acetyltransferase that is essential for growth in yeast.

  • E. SmithA. Eisen C. Allis
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
A yeast ORF with homology to MYST family members and show it possesses histone acetyltransferase activity is expressed and unlike the other MYSTfamily members in Saccharomyces cerevisiae this gene is essential for growth.

Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo.

The identified multiple substitution mutations are identified that eliminated completely Gcn5's ability to potentiate transcriptional activation in vivo and support previous arguments that nucleosomal histones are among the physiological substrates of acetylation by GCN5.

Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines

It is reported that Gcn5p acetylates histones H3 and H4 non-randomly at specific lysines in the amino-terminal domains, and it is demonstrated that lysine 9 is the preferred position of acetylation in newly synthesized yeast H3 in vivo.

Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo.

It is demonstrated that the HAT activity of Gcn5p is critical for transcriptional activation of target genes in vivo, the first in vivo evidence that promoter-specific histone acetylation, catalyzed by functional Gcn 5p, plays a critical role in gene activation.

HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription.

The characterized yeast histone deacetylase complexes demonstrate that histone acetylation state has a role in regulating both heterochromatic silencing and regulated gene expression.