Evidence of a MOF histone acetyltransferase-containing NSL complex in<i>C. elegans</i>

Hoe, Matthew; Nicholas, Hannah R.

doi:10.4161/21624054.2014.982967

Cited by 8 publications

(9 citation statements)

References 51 publications

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“…We identified the MOF homologue MYS-2, OGT-1, MCRS-1 and the NSL2 and NSL3 homologues SUMV-1 and SUMV-2, respectively. Homologues of two other NSL components found in other organisms, MBD-R2/PHF20 and NSL1/KANSL1, are not found in the C. elegans genome (80). Therefore, as in other species, C. elegans WDR-5.1 is found in the NSL complex as well as COMPASS/MLL complexes.…”

Section: Resultsmentioning

confidence: 99%

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

Beurton

Stempor

Caron

et al. 2019

Nucleic Acids Research

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The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute to context dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between Caenorhabditis elegans CFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex. Supporting a functional connection, we find that mutants of COMPASS and SIN3 complex components genetically interact and have similar phenotypic defects including misregulation of common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3S HDAC complex at promoters.

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Section: Resultsmentioning

confidence: 99%

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

Beurton

Stempor

Caron

et al. 2019

Nucleic Acids Research

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“…OGT-1 is the ortholog of the human O-GlcNAc transferase OGT and plays a role in nutrient sensing and insulin signaling pathways, both of which are involved in lifespan regulation in C. elegans (Hanover et al 2005; Love et al 2010; Mondoux et al 2011; Radermacher et al 2014). In addition, OGT-1 can be part of histone acetyltransferase-containing protein complexes [Hoe and Nicholas 2014; reviewed by Gambetta and Müller (2015)], suggesting a direct involvement in chromatin regulation. In summary, our IP-MS identified novel MRG-1 interactions and excludes the possibility of direct MRG-1 association with PRC2 or MES-4.…”

Section: Resultsmentioning

confidence: 99%

“…Yet, the Drosophila ortholog of OGT-1 was initially identified as a member of Polycomb group (PcG) class proteins, which are repressive chromatin regulators (Ingham 1984). Additional studies suggest that OGT-1 can be part of histone acetyltransferase-containing protein complexes [Hoe and Nicholas 2014; reviewed by Gambetta and Müller (2015)]. We identified the H3K9 methyltransferase SET-26 as one of the most consistent MRG-1–interacting proteins (Greer et al 2014).…”

Section: Discussionmentioning

confidence: 99%

MRG-1/MRG15 Is a Barrier for Germ Cell to Neuron Reprogramming in Caenorhabditis elegans

et al. 2018

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Chromatin regulators play important roles in the safeguarding of cell identities by opposing the induction of ectopic cell fates and, thereby, preventing forced conversion of cell identities by reprogramming approaches. Our knowledge of chromatin regulators acting as reprogramming barriers in living organisms needs improvement as most studies use tissue culture. We used Caenorhabditis elegans as an in vivo gene discovery model and automated solid-phase RNA interference screening, by which we identified 10 chromatin-regulating factors that protect cells against ectopic fate induction. Specifically, the chromodomain protein MRG-1 safeguards germ cells against conversion into neurons. MRG-1 is the ortholog of mammalian MRG15 (MORF-related gene on chromosome 15) and is required during germline development in C. elegans. However, MRG-1’s function as a barrier for germ cell reprogramming has not been revealed previously. Here, we further provide protein-protein and genome interactions of MRG-1 to characterize its molecular functions. Conserved chromatin regulators may have similar functions in higher organisms, and therefore, understanding cell fate protection in C. elegans may also help to facilitate reprogramming of human cells.

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“…The NSL complex is highly conserved, and NSL orthologs have been identified in a range of organisms including C. elegans and D. rerio (Fig B). There are four core members of the NSL complex, KANSL1 (also referred to as MSL1v1 ), KANSL2, KANSL3, and PHF20, which have only been identified as part of the NSL complex to date (Fig C).…”

Section: Constituents Of the Nsl Complexmentioning

confidence: 99%

The non‐specific lethal ( NSL ) complex at the crossroads of transcriptional control and cellular homeostasis

2019

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The functionality of chromatin is tightly regulated by post‐translational modifications that modulate transcriptional output from target loci. Among the post‐translational modifications of chromatin, reversible ε‐lysine acetylation of histone proteins is prominent at transcriptionally active genes. Lysine acetylation is catalyzed by lysine acetyltransferases (KATs), which utilize the central cellular metabolite acetyl‐CoA as their substrate. Among the KATs that mediate lysine acetylation, males absent on the first (MOF/KAT8) is particularly notable for its ability to acetylate histone 4 lysine 16 (H4K16ac), a modification that decompacts chromatin structure. MOF and its non‐specific lethal (NSL) complex members have been shown to localize to gene promoters and enhancers in the nucleus, as well as to microtubules and mitochondria to regulate key cellular processes. Highlighting their importance, mutations or deregulation of NSL complex members has been reported in both human neurodevelopmental disorders and cancer. Based on insight gained from studies in human, mouse, and Drosophila model systems, this review discusses the role of NSL‐mediated lysine acetylation in a myriad of cellular functions in both health and disease. Through these studies, the importance of the NSL complex in regulating core transcriptional and signaling networks required for normal development and cellular homeostasis is beginning to emerge.

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Evidence of a MOF histone acetyltransferase-containing NSL complex inC. elegans

Cited by 8 publications

References 51 publications

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

MRG-1/MRG15 Is a Barrier for Germ Cell to Neuron Reprogramming in Caenorhabditis elegans

The non‐specific lethal ( NSL ) complex at the crossroads of transcriptional control and cellular homeostasis

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