alexa Human Sin3 deacetylase and trithorax-related Set1 Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1.
Genetics & Molecular Biology

Genetics & Molecular Biology

Fungal Genomics & Biology

Author(s): Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W

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Abstract The abundant and chromatin-associated protein HCF-1 is a critical player in mammalian cell proliferation as well as herpes simplex virus (HSV) transcription. We show here that separate regions of HCF-1 critical for its role in cell proliferation associate with the Sin3 histone deacetylase (HDAC) and a previously uncharacterized human trithorax-related Set1/Ash2 histone methyltransferase (HMT). The Set1/Ash2 HMT methylates histone H3 at Lys 4 (K4), but not if the neighboring K9 residue is already methylated. HCF-1 tethers the Sin3 and Set1/Ash2 transcriptional regulatory complexes together even though they are generally associated with opposite transcriptional outcomes: repression and activation of transcription, respectively. Nevertheless, this tethering is context-dependent because the transcriptional activator VP16 selectively binds HCF-1 associated with the Set1/Ash2 HMT complex in the absence of the Sin3 HDAC complex. These results suggest that HCF-1 can broadly regulate transcription, both positively and negatively, through selective modulation of chromatin structure.
This article was published in Genes Dev and referenced in Fungal Genomics & Biology

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