Roles of common subunits within distinct multisubunit complexes

Nakabayashi, Yu; Kawashima, Seiichiro; Enomoto, Takemi; Seki, Masayuki; Horikoshi, Masami

doi:10.1073/pnas.1316433111

Cited by 9 publications

(7 citation statements)

References 36 publications

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“…We expressed H2A and H2B as a single-chain (one peptide) (Fig. 6a ) using a similar strategy to one used in yeast 54 , to determine if H2BK20ac is required on the macroH2A1/H2B heterodimer or on the nucleosome-bound H2B as a genomic beacon. We generated single-chain constructs with just the HFD of macroH2A1 as we previously showed the macroH2A1 HFD was sufficient for accurate deposition (Fig.…”

Section: Resultsmentioning

confidence: 99%

MacroH2A1 chromatin specification requires its docking domain and acetylation of H2B lysine 20

Ruiz

Gamble

2018

Nat Commun

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The histone variant macroH2A1 localizes to two functionally distinct chromatin subtypes marked by either H3K27me3 or H2B acetylations, where it is thought to directly regulate transcription. The recent finding, that macroH2A1 regulates mitochondrial respiration by globally dampening PARP activity, requires the field to re-evaluate which functions of macroH2A1 are due to global effects on cellular metabolism and which are direct effects determined by macroH2A1 chromatin localization. Here, we demonstrate macroH2A1 incorporation into H2B-acetylated chromatin requires a feature in its histone-fold domain, distinguishing this process from incorporation into H3K27me3-containing chromatin in which multiple features of macroH2A1 are sufficient for targeting. In addition, we identify H2BK20 acetylation as a critical modification required to target macroH2A1 to H2B-acetylated chromatin. Our findings have allowed us to definitively establish that macroH2A1’s regulation of an important transcriptional program, the senescence-associated secretory phenotype (SASP), requires its accurate genomic localization.

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Section: Resultsmentioning

confidence: 99%

MacroH2A1 chromatin specification requires its docking domain and acetylation of H2B lysine 20

Ruiz

Gamble

2018

Nat Commun

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“…For this reason, modifications on H2A/H2B have been less studied than those on H3 and H4 in the epigenetics field. However, many studies acknowledge the potential impact that modifications on H2B can have on chromatin dynamics 33 . Some forms of epigenetic modifications alter the chromatin structure to alter gene expression, which affects pathological processes in a multitude of disease conditions related to tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of a histone family gene signature for predicting the prognosis of cervical cancer patients

Tian

Gao

et al. 2017

Sci Rep

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Heterogeneity in terms of tumor characteristics, prognosis, and survival among cancer patients is an unsolved issue. Here, we systematically analyzed the aberrant expression patterns of cervical cancer using RNA-Seq data from The Cancer Genome Atlas (TCGA). We incorporated gene profiling, molecular signatures, functional and pathway information with gene set enrichment and protein-protein interaction (PPI) network analysis, to identify sub-networks of genes. Those identified genes relating to DNA replication and DNA repair-mediated signaling pathways associated with systemic lupus erythematosus (SLE). Next, we combined cross-validated prognostic scores to build an integrated prognostic model for survival prediction. The combined approach revealed that the DNA repair-mediated including the functional interaction module of 18 histone genes (Histone cluster 1 H2A, B and H4), were significantly correlated with the survival rate. Furthermore, five of these histone genes were highly expressed in three cervical cancer cohorts from the Oncomine database. Comparison of high and low histone variant-expressing human cervical cancer cell lines revealed different responses to DNA damage, suggesting protective functions of histone genes against DNA damage. Collectively, we provide evidence that two SLE-associated gene sets (HIST1H2BD and HIST1H2BJ; and HIST1H2BD, HIST1H2BJ, HIST1H2BH, HIST1H2AM and HIST1H4K) can be used as prognostic factors for survival prediction among cervical cancer patients.

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“…Second, we argue that because complexes with already annotated functions are preferentially cited in the literature, an increasing fraction of research is focused on already well-known entities, introducing a strong bias in contents. Third, some proteins are multifunctional and perform unique tasks in the context of different protein complexes, thereby highlighting that the function of protein complexes is not simply the aggregate of their subunits’ functions [ 54–56 ]. As a case in point, a brief examination of the GO terms annotated for whole protein complexes in the CORUM database compared to each individual subunit’s GO term annotations in the QuickGO database [ 42 ] showed that 2155 (61.4%), 319 (9.1%) and 169 (4.8%) protein complexes contained at least one novel biological process, molecular function, or cellular component term, respectively, that was not annotated for any individual subunit’s QuickGO entry.…”

Section: Discussionmentioning

confidence: 99%

PCfun: a hybrid computational framework for systematic characterization of protein complex function

Sharma

Fossati

Ciuffa

et al. 2022

Briefings in Bioinformatics

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In molecular biology, it is a general assumption that the ensemble of expressed molecules, their activities and interactions determine biological function, cellular states and phenotypes. Stable protein complexes—or macromolecular machines—are, in turn, the key functional entities mediating and modulating most biological processes. Although identifying protein complexes and their subunit composition can now be done inexpensively and at scale, determining their function remains challenging and labor intensive. This study describes Protein Complex Function predictor (PCfun), the first computational framework for the systematic annotation of protein complex functions using Gene Ontology (GO) terms. PCfun is built upon a word embedding using natural language processing techniques based on 1 million open access PubMed Central articles. Specifically, PCfun leverages two approaches for accurately identifying protein complex function, including: (i) an unsupervised approach that obtains the nearest neighbor (NN) GO term word vectors for a protein complex query vector and (ii) a supervised approach using Random Forest (RF) models trained specifically for recovering the GO terms of protein complex queries described in the CORUM protein complex database. PCfun consolidates both approaches by performing a hypergeometric statistical test to enrich the top NN GO terms within the child terms of the GO terms predicted by the RF models. The documentation and implementation of the PCfun package are available at https://github.com/sharmavaruns/PCfun. We anticipate that PCfun will serve as a useful tool and novel paradigm for the large-scale characterization of protein complex function.

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Roles of common subunits within distinct multisubunit complexes

Cited by 9 publications

References 36 publications

MacroH2A1 chromatin specification requires its docking domain and acetylation of H2B lysine 20

MacroH2A1 chromatin specification requires its docking domain and acetylation of H2B lysine 20

Identification of a histone family gene signature for predicting the prognosis of cervical cancer patients

PCfun: a hybrid computational framework for systematic characterization of protein complex function

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