Black arrows, conserved ZN-finger residues. manuscript, sequencing data have been deposited in GEO under accession codes “type”:”entrez-geo”,”attrs”:”text”:”GSE112951″,”term_id”:”112951″GSE112951 (ChIP-seq) and “type”:”entrez-geo”,”attrs”:”text”:”GSE112950″,”term_id”:”112950″GSE112950 (RNA-seq). All datasets from this study are combined in a super-series (“type”:”entrez-geo”,”attrs”:”text”:”GSE112952″,”term_id”:”112952″GSE112952). All other data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 4 and 5. The most relevant bioinformatics source BQ-788 code files for Figures 2 and 7 have been provided as individual files. The following datasets were generated: Clara Bourbousse, Ouardia Ait-Mohamed. 2018. Nassrallah, Rouge et al., ChIP-seq datasets. NCBI Gene Expression Omnibus. GSE112951 Clara Bourbousse, Ouardia Ait-Mohamed, Martin Rouge, Fredy Barneche. 2018. Nassrallah, Rouge et al., ChIP-seq and RNA-seq super-series. NCBI Gene Expression Omnibus. GSE112952 Bourbousse C, AitMohamed O, Rouge M, Barneche F. 2018. Nassrallah, Rouge et al., RNA-seq datasets. NCBI Gene Expression Omnibus. GSE112950 Abstract DE-ETIOLATED 1 (DET1) is an evolutionarily conserved component of the ubiquitination machinery that mediates the destabilization of key regulators of cell differentiation and proliferation in multicellular organisms. In this study, we provide evidence from Arabidopsis that DET1 is essential for the regulation of histone H2B monoubiquitination (H2Bub) over most genes by controlling the stability of a deubiquitination module (DUBm). In contrast with yeast BQ-788 and metazoan DUB modules that are associated with the large SAGA complex, the Arabidopsis DUBm only comprises three proteins (hereafter named SGF11, ENY2 and UBP22) and appears to act independently as a major H2Bub deubiquitinase activity. Our study further unveils that DET1-DDB1-Associated-1 (DDA1) protein interacts with SGF11 null mutations are lethal in plants (Misra et al., 1994; Pepper et al., 1994), Drosophila (Berloco et al., 2001) and Human (Wertz et al., 2004). However, viable Arabidopsis knockdown alleles identified in genetic screens for mutant plants displaying a constitutive photomorphogenic phenotype (i.e. de-etiolated) have unveiled that DET1 is a central integrator of light signaling in plants (Chory et al., 1989; Pepper et al., 1994). The Arabidopsis mutation affects the expression of thousands of nuclear genes (Ma et al., 2003; Schroeder et al., 2002), partly because proteolytic degradation of the proto-photomorphogenic transcription factor HY5 is abolished in this background, thereby mimicking the presence of light on the transcriptional program (Osterlund et al., 2000). In humans, DET1 also controls the stability of cell proliferation factors such as the Cdt1 DNA replication-licensing factor (Pick et al., 2007) and the proto-oncogenic transcription factor c-Jun (Wertz et al., 2004). Accordingly, a currently accepted model in both plants and animals is that DET1 is an atypical DAMAGED DNA BINDING PROTEIN 1 (DDB1)-CULLIN4 (CUL4) Associated Factor (DCAF) acting with the small DDA1 (DET1-DDB1-Associated 1) protein to provide specificity to one or more E3 CUL4-RING ubiquitin ligases (CRL4) (Chory, 2010; Lau and Deng, 2012). For this activity, DET1 and DDA1, together with DDB1 and CONSTITUTIVE PHOTOMORPHOGENIC 10 (COP10) proteins, constitute a substrate adaptor module (COP10-DET1-DDB1-DDA1; hereafter termed C3D) BQ-788 within CRL4 complexes (Irigoyen et al., 2014; Pick et al., 2007). C3D binding to the CUL4 scaffolding protein is mediated by the core adaptor subunit DDB1 whereas the E2 ubiquitin conjugase variant COP10 likely acts to increase the activity of CRL4 complexes towards specific protein targets (Lau and Deng, 2012). Photomorphogenesis is a developmental switch that initiates upon the first perception of light by young plants reaching the soil surface. This transition triggers the launching of organ growth and the establishment Rabbit Polyclonal to SLC9A3R2 of photosynthesis, most notably through the BQ-788 differentiation of primary leaf (cotyledon) cells (reviewed in?[Casal, 2013; Seluzicki et al., 2017; Wu, 2014]). The process involves changes at transcriptomic, epigenomic and nuclear architecture levels (Bourbousse et al., 2015; Charron et al., 2009; Sullivan et al., 2014). While several chromatin modifiers are known to influence light-responsive gene expression, the first direct link between light signaling and chromatin came from the discovery that DET1 has high affinity for nucleosomal histone H2B in vitro and in vivo (Benvenuto.