Histone Acetyltransferases as Regulators of Nonhistone Proteins: The Role of Interferon Regulatory Factor Acetylation on Gene Transcription

Atsuko Masumi

doi:10.1155/2011/640610

Abstract

When studying transcription factors, it is necessary to investigate posttranslational modifications. Histone acetyltransferases (HATs) are typical of the modification enzymes involved in chromatin regulation. HATs acetylate the transcription factors (nonhistone proteins) as well as histones. Interferon regulatory factors (IRFs) are transcription factors that bind to the interferon regulatory element (IRF-E) and are involved in regulating cell growth, differentiation, and the immune and hematopoietic systems. During the process of binding to a specific DNA element, IRFs also bind to coactivators such as HATs and become modified. This review looks at how IRFs associate with HATs, p300, and PCAF, and thereby contribute to transcriptional activation.

Highlights

Cellular proteins are posttranslationally modified by various mechanisms, including acetylation, deacetylation, phosphorylation, and methylation
As we will describe below, Interferon regulatory factors (IRFs) are transcription factors that have been shown to be acetylated by histone acetyltransferases (HATs) [6, 7]
We previously demonstrated that IRF-1 and IRF-2 both interact with the histone acetyltransferase PCAF in vitro and that this interaction plays an important role in controlling transcription from relevant promoters [6, 13, 14]

Summary

Introduction

Cellular proteins are posttranslationally modified by various mechanisms, including acetylation, deacetylation, phosphorylation, and methylation. The acetylation of several transcription factors may regulate their function, by multiple mechanisms, including the modification of DNA binding ability, secondary protein-protein interactions, protein half-life, and protein localization. These events, in turn, can influence DNA repair, cell cycle progression, apoptosis, and various signaling pathways. As we will describe below, IRFs are transcription factors that have been shown to be acetylated by histone acetyltransferases (HATs) [6, 7] Such IRFs modifications are associated with cell growth and differentiation as well as the IFN response. HAT proteins form multiple complexes and are recruited to chromatin to acetylate histones or to transcription factors. In terms of IRF regulation by acetylation, PCAF and CBP/p300 play especially important roles

The IRF Family of Transcription Factors

IRF-3 and IRF-7

HATs in Interferon Signaling

HDAC and IRF

Future Direction