HBO1 HAT Complexes Target Chromatin throughout Gene Coding Regions via Multiple PHD Finger Interactions with Histone H3 Tail

Laval University Cancer Research Center, Hôtel-Dieu de Québec (CHUQ), Quebec City, QC, Canada.
Molecular cell (Impact Factor: 14.02). 02/2009; 33(2):257-65. DOI: 10.1016/j.molcel.2009.01.007
Source: PubMed


The HBO1 HAT protein is the major source of histone H4 acetylation in vivo and has been shown to play critical roles in gene regulation and DNA replication. A distinctive characteristic of HBO1 HAT complexes is the presence of three PHD finger domains in two different subunits: tumor suppressor proteins ING4/5 and JADE1/2/3. Biochemical and functional analyses indicate that these domains interact with histone H3 N-terminal tail region, but with a different specificity toward its methylation status. Their combinatorial action is essential in regulating chromatin binding and substrate specificity of HBO1 complexes, as well as cell growth. Importantly, localization analyses on the human genome indicate that HBO1 complexes are enriched throughout the coding regions of genes, supporting a role in transcription elongation. These results underline the importance and versatility of PHD finger domains in regulating chromatin association and histone modification crosstalk within a single protein complex.

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    • "To determine whether there was a specific region within the H3 N terminus sufficient for the interaction , pull-down assays were performed using a series of biotinylated peptides spanning the tail region. In contrast to JADE1 PZP , which bound as expected to a peptide spanning amino acids 1–21 (H3 1–21 ; the very N terminus of H3) (Saksouk et al., 2009), neither AF10 PZP nor AF17 PZP bound the H3 1–21 peptide but rather bound to a peptide spanning amino acids 15–34 (H3 15–34 ; Figure 1D). AF10 PZP , in addition to being sufficient, is also necessary for full-length AF10 to bind H3 15–34 (Figure S1B). "
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    • "This interaction is very sensitive to the methylation status of H3K4, as it is disrupted even by monomethylation (Saksouk et al. 2009; Qin et al. 2011; Lalonde et al. 2013). Interestingly, the regulated presence of the ING subunit with its PHD reverses this sensitivity to H3K4me (Saksouk et al. 2009; Avvakumov et al. 2012; Lalonde et al. 2013). In addition to the PZP domain, the BRPF scaffold subunit of the HBO1 and MOZ/MORF HAT complexes contains a PWWP domain that binds H3K36me3 and regulates binding to chromatin in vivo (Fig. 2A; Laue et al. 2008; Vezzoli et al. 2010). "
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    • "The histone acetyltransferase complex with HBO1 as a component may exist in different forms. Activity of one of these forms, which contains ING4/5 proteins, is considerably increased in the presence of trimethylated H3K4 owing to a high affinity of ING proteins for this particular modification (Saksouk et al. 2009). Thus, H3K4me3 may enhance HBO1 recruiting to the origin. "
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