Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro.

Abstract

Core histones isolated from normal and butyrate‐treated HeLa cells have been reconstituted into nucleosome cores in order to analyze the role of histone acetylation in enhancing transcription factor binding to recognition sites in nucleosomal DNA. Moderate stimulation of nucleosome binding was observed for the basic helix‐loop‐helix factor USF and the Zn cluster DNA binding domain factor GAL4‐AH using heterogeneously acetylated histones. However, by coupling novel immunoblotting techniques to a gel retardation assay, we observed that nucleosome cores containing the most highly acetylated forms of histone H4 have the highest affinity for these two transcription factors. Western analysis of gel‐purified USF‐nucleosome and GAL4‐AH‐nucleosome complexes demonstrated the predominant presence of acetylated histone H4 relative to acetylated histone H3. Immunoprecipitation of USF‐nucleosome complexes with anti‐USF antibodies also demonstrated that these complexes were enriched preferentially in acetylated histone H4. These data show that USF and GAL4‐AH preferentially interact with nucleosome cores containing highly acetylated histone H4. Acetylation of histone H4 thus appears to play a primary role in the structural changes that mediate enhanced binding of transcription factors to their recognition sites within nucleosomes.

Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation

“…Histones are subject to a variety of posttranslational modifications, of which the best studied is acetylation (for review, see Turner, 2005). Histone acetylation alters chromatin structure (Norton et al, 1989) and increases accessibility for transcriptional regulatory proteins (Vettese-Dadey et al, 1996). The steady-state levels of histone acetylation are the product of proteins with histone acetyltransferase (HAT) activity that add acetyl groups to histones and proteins with histone deacetylase (HDAC) activity that remove acetyl groups.…”

Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation

“…Acetylation occurs at lysine residues on the amino-terminal tails of the histones, thereby neutralizing their positive charge and decreasing their affinity for DNA (Hong et al, 1993). As a consequence, histone acetylation alters the nucleosome conformation (Norton et al, 1989), and this can increase the accessibility of transcription regulatory proteins to the chromatin template (Lee et al, 1993;Vettese-Dadey et al, 1996). A number of transcriptional coactivators, including GCN5 , TAF250 (Mizzen et al, 1996), CBP/p300 (Ogryzko et al, 1996), PCAF (Yang et al, 1996b), ACTR (Chen et al, 1997), Tip60 (Yamamoto and Horikoshi, 1997), and SRC-1 (Spencer et al, 1997), possess intrinsic histone acetyltransferase (HAT) activity or have the ability to recruit proteins with such activity.…”

Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice

“…Site-specific acetylation or deacetylation of nucleosomal histones H3 and H4 is central to the switch between permissive and repressive chromatin structure and thus activation or repression of transcription [28]. With a high affinity for upstream transcription factor binding [29], H3 and H4 are the core histones with high levels of acetylation at the active transcriptional loci [30]. It would be of great interest to determine whether the presumed diminished intracellular ROS production in OE islets enhances Pdx1 transcription via hyper-acetylating H3 and H4 in its proximal promoter region, causing hypertrophy of beta cells and overproduction of insulin.…”