ADCP1: a novel plant H3K9me2 reader

C. Jake Harris, Steven E. Jacobsen
2018 Cell Research  
H3K9 methylation is an epigenetic mark associated with heterochromatin. Zhao and colleagues characterize a novel H3K9me reader protein, ADCP1, that plays a role in heterochromatin maintenance and shows functional similarities to animal HP1 proteins. Eukaryotic genomes are broadly compartmentalized into nonoverlapping transcriptionally permissive 'euchromatic' and repressed 'heterochromatic' regions. These regions are decorated by a suite of distinct epigenetic marks, which help to reinforce and
more » ... demarcate their transcriptional state. In Arabidopsis, the majority of heterochromatin is confined to the central portion of each chromosome near the centromere, and this spatial separation from euchromatin makes it an attractive model to study epigenetic states. Di-methylation of lysine 9 of histone H3 (H3K9me2) is a key epigenetic mark associated with heterochromatin in plants, functionally analogous to H3K9me3 in mammals. 1 A large body of work has described epigenetic feedback loops in Arabidopsis, which act to maintain H3K9me2, together with DNA methylation. 1 For instance, three partially redundant proteins, KRYPTONITE (KYP, also known as SUVH4), SUVH5 and SUVH6 work together with CHROMOMETHYLASE3 (CMT3) to form a selfreinforcing feedback loop for coincident maintenance of CHG methylation and H3K9me2. The SRA domain of KYP binds to methylated DNA, and establishes H3K9me2 via its C-terminal SET histone methyltransferase domain. Reciprocally, the N-terminal BAH and chromo domains of CMT3 bind to H3K9me2, and the Cterminal DNA methyltransferase domain establishes CHG methylation. KYP/SUHV5/SUVH6 also operate in a similar feedback loop with CMT2 to maintain CHH methylation. Because these proteins contain both heterochromatic 'reader' and 'writer' domains, they form straightforward epigenetic feedback loops. Much less is known about factors that act downstream of H3K9me2 to enforce transcriptional repression. Zhao and colleagues describe a novel protein, ADCP1, which by its domain structure, appears to have a strict H3K9me2 'reader' function. 2 However, the authors show that ADCP1 also clearly contributes to H3K9me2 and DNA methylation maintenance, although it is currently unclear whether these effects are direct or indirect. Importantly, the adcp1 mutant also shows derepression of many transposons marked with H3K9me2, and shows a partial decondensation of the chromocenters (dense nuclear bodies containing the pericentromeric heterochromatin). Interestingly, a recent paper by Zhang and colleagues also identified the same protein from a different proteomics screen (calling it 'AGDP1′), and reported largely similar results. 3 ADCP1 was initially identified from a previously published labon-chip histone reader screen by the same research group. 4
doi:10.1038/s41422-018-0119-2 pmid:30514899 pmcid:PMC6318331 fatcat:ue7xjgvu4bedhaphbsry4nevoe