The histone chaperone TAF-I/SET/INHAT is required for transcription in vitro of chromatin templates

Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 02/2005; 25(2):797-807. DOI: 10.1128/MCB.25.2.797-807.2005
Source: PubMed


To uncover factors required for transcription by RNA polymerase II on chromatin, we fractionated a mammalian cell nuclear extract. We identified the histone chaperone TAF-I (also known as INHAT [inhibitor of histone acetyltransferase]), which was previously proposed to repress transcription, as a potent activator of chromatin transcription responsive to the vitamin D3 receptor or to Gal4-VP16. TAF-I associates with chromatin in vitro and can substitute for the related protein NAP-1 in assembling chromatin onto cloned DNA templates in cooperation with the remodeling enzyme ATP-dependent chromatin assembly factor (ACF). The chromatin assembly and transcriptional activation functions are distinct, however, and can be dissociated temporally. Efficient transcription of chromatin assembled with TAF-I still requires the presence of TAF-I during the polymerization reaction. Conversely, TAF-I cannot stimulate transcript elongation when added after the other factors necessary for assembly of a preinitiation complex on naked DNA. Thus, TAF-I is required to facilitate transcription at a step after chromatin assembly but before transcript elongation.

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    • "SET (Fig. 3c) has been suggested to function in multiple critical cellular pathways, including transcription (Gamble et al., 2005; Matsumoto et al., 1995; Miyamoto et al., 2003; Suzuki et al., 2003), replication (Matsumoto et al., 1995), and apoptosis (Fan et al., 2003). The precise function of SET in transcription, however, is controversial, as it has been shown to inhibit transcription by physically blocking acetylation of the histone tails (Seo et al., 2001), but also acts as an activator of transcription on chromatin templates (Gamble et al., 2005). SET can substitute for Nap1 in chromatin assembly and disassembly reactions in vitro (Kawase et al., 1996; Okuwaki et al., 2005), which is not surprising given their structural similarity. "
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