Abstract
The plant homeodomain (PHD) finger is found in many chromatin-associated proteins and functions to recruit effector proteins to chromatin through its ability to bind both methylated and unmethylated histone residues. Here, we show that the dual PHD fingers of Rco1, a member of the Rpd3S histone deacetylase complex recruited to transcribing genes, operate in a combinatorial manner in targeting the Rpd3S complex to histone H3 in chromatin. Although mutations in either the first or second PHD finger allow for Rpd3S complex formation, the assembled complexes from these mutants cannot recognize nucleosomes or function to maintain chromatin structure and prevent cryptic transcriptional initiation from within transcribed regions. Taken together, our findings establish a critical role of combinatorial readout in maintaining chromatin organization and in enforcing the transcriptional fidelity of genes.
Highlights
Post-translational modifications on histone proteins play a critical role in many DNA-templated processes, the control of gene transcription
Consistent with this finding, we demonstrate that mutation of either PHD finger of Rco1 (PHD1) or PHD2 leads to chromatin and transcriptional fidelity defects
Rco1 Contains Two plant homeodomain (PHD) Fingers That Bind to the N Terminus of H3—Rco1 is a unique member of the Rpd3S complex, which is defined by a N-terminal PHD finger followed by an autoinhibitory domain; a Sin3 interaction domain, which associates with the MRG domain of Eaf3 [11]; and a second C-terminal PHD finger (Fig. 1A)
Summary
Rpd3S, an histone deacetylase that functions in a co-transcriptional manner, has five conserved chromatin-binding domains: a chromodomain in Eaf, which recognizes Set2mediated histone H3 lysine 36 methylation (H3K36me) (6 – 8), and four plant homeodomains (PHDs), two per copy of Rco, which has recently been shown to form a homodimer in Rpd3S (see Fig. 1A) [9]. PHD1 is thought to engage H3 on one nucleosome, whereas the chromodomain of Eaf recognizes H3K36me on a neighboring nucleosome, allosterically activating the deacetylase activity of Rpd3 [11, 12] This activity is necessary to enforce chromatin integrity and transcriptional fidelity across the transcribed regions of genes, thereby preventing the formation of pervasive cryptic unstable transcripts and stable untranslated transcripts [6, 10, 13, 14]. Combinatorial Histone Readout by the Dual PHD Fingers of Rco data unveil a critical role for two adjacent PHD fingers in coordinating Rpd3S recruitment and function
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