Article

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: 14.46). 02/2009; 33(2):257-65. DOI: 10.1016/j.molcel.2009.01.007
Source: PubMed

ABSTRACT 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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    • "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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    • "Jade-1 is of particular interest as it is a key player in H4 acetylation at active genes [45]. It was earlier shown that in the presence of the human tumour suppressor proteins ING4 and ING5, Jade-1 targets the chromatin through interaction with H3K4me3 modifications [46]. Our finding may therefore hint to an epigenomic feed-forward loop based on cross-talk between H4 acetylation and H3K4 methylation. "
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    • "H4 acetylation occurs at multiple lysine sites, which often results in chromatin remodelling and transcriptional activation (Shahbazian and Grunstein, 2007; Campos and Reinberg, 2009; Suganuma and Workman, 2011). The HBO1 (human acetylase binding to ORC1) complex is responsible for the acetylation of histone H4 at K5, K8, and K12 sites, in which Jade1, a PHD zinc finger protein, modulates the histone acetyltransferase activity (Tzouanacou et al, 2003; Foy et al, 2008; Saksouk et al, 2009). In addition to HBO1, the histone acetylase MOF also mediated the K16 acetylation of histone H4 after DNA damage. "
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