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Free keywords:
gene transcription; chromatin modification
Abstract:
Bypass of Ess1 (Bye1) is a nuclear protein with a domain resembling
the central domain in the transcription elongation factor
TFIIS. Here we show that Bye1 binds with its TFIIS-like domain
(TLD) to RNA polymerase (Pol) II, and report crystal structures of
the Bye1 TLD bound to Pol II and three different Pol II–nucleic acid
complexes. Like TFIIS, Bye1 binds with its TLD to the Pol II jaw and
funnel. In contrast to TFIIS, however, it neither alters the conformation
nor the in vitro functions of Pol II. In vivo, Bye1 is recruited
to chromatin via its TLD and occupies the 5′-region of active
genes. A plant homeo domain (PHD) in Bye1 binds histone H3
tails with trimethylated lysine 4, and this interaction is enhanced
by the presence of neighboring posttranslational modifications
(PTMs) that mark active transcription and conversely is impaired
by repressive PTMs. We identify putative human homologs of
Bye1, the proteins PHD finger protein 3 and death-inducer obliterator,
which are both implicated in cancer. These results establish
Bye1 as the founding member of a unique family of chromatin
transcription factors that link histones with active PTMs to transcribing
Pol II.
