Wiki-Pi: A Web-Server of Annotated Human Protein-Protein Interactions to Aid in Discovery of Protein Function

Orii, Naoki; Ganapathiraju, Madhavi K.

doi:10.1371/journal.pone.0049029

Cited by 75 publications

(62 citation statements)

References 39 publications

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“…We then identified eight TFs that are associated with these distal z-HPRs (Table 2). Of note, among these identified TFs, four were previously reported to physically interact [TAL1-LIM domain only 2 (LMO2), nescient helix loop helix 1 (NHLH1)-LMO2, and TAL1-epididymal sperm binding protein 1 (ELSPB1)], suggesting that they cooperate in regulating H3K27me3 variability and Polycomb activities (44). Importantly, our analysis identified TAL1, a principal regulator of hematopoietic development (39), as a candidate regulator of ProEspecific H3K27me3 variability (Fig.…”

Section: Computational Analysis Identifies Tal1 In Regulating H3k27me3mentioning

confidence: 58%

Analysis of chromatin-state plasticity identifies cell-type–specific regulators of H3K27me3 patterns

Pinello

Orkin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Chromatin states are highly cell-type-specific, but the underlying mechanisms for the establishment and maintenance of their genome-wide patterns remain poorly understood. Here we present a computational approach for investigation of chromatin-state plasticity. We applied this approach to investigate an ENCODE ChIP-seq dataset profiling the genome-wide distributions of the H3K27me3 mark in 19 human cell lines. We found that the high plasticity regions (HPRs) can be divided into two functionally and mechanistically distinct subsets, which correspond to CpG island (CGI) proximal or distal regions, respectively. Although the CGI proximal HPRs are typically associated with continuous variation across different cell-types, the distal HPRs are associated with binary-like variations. We developed a computational approach to predict putative cell-type-specific modulators of H3K27me3 patterns and validated the predictions by comparing with public ChIPseq data. Furthermore, we applied this approach to investigate mechanisms for poised enhancer establishment in primary human erythroid precursors. Importantly, we predicted and experimentally validated that the principal hematopoietic regulator T-cell acute lymphocytic leukemia-1 (TAL1) is involved in regulating H3K27me3 variations in collaboration with the transcription factor growth factor independent 1B (GFI1B), providing fresh insights into the context-specific role of TAL1 in erythropoiesis. Our approach is generally applicable to investigate the regulatory mechanisms of epigenetic pathways in establishing cellular identity.polycomb | hematopoiesis | histone modifications | motifs

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Section: Computational Analysis Identifies Tal1 In Regulating H3k27me3mentioning

confidence: 58%

Analysis of chromatin-state plasticity identifies cell-type–specific regulators of H3K27me3 patterns

Pinello

Orkin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…To study the molecular mechanisms underlying the proliferative phenotype of KPNA1 KO satellite cells, we mined a protein-protein interaction database (Wiki-Pi) [46] based on verified data, and identified 32 KPNA1-interacting proteins. We demonstrated that one of these KPNA1 cargo proteins, p27 (CDKN1B, a cell cycle inhibitor protein), was localized to the cytoplasm in a greater proportion of KPNA1 KO satellite cells than WT although both genotypes showed similar transcript levels.…”

Section: Discussionmentioning

confidence: 99%

“…In order to gain mechanistic insights into the proliferative phenotype of KPNA1 KO satellite cells, we searched for potential cargo proteins of KPNA1 from a protein-protein interaction database (Wiki-Pi) [46]. In humans, 32 proteins are known to interact with KPNA1 and these proteins were grouped into 4 categories by Gene Ontology analysis (Fig.…”

Section: Reduced Nuclear Translocation Of P27 and Increasedmentioning

confidence: 99%

Karyopherin Alpha 1 Regulates Satellite Cell Proliferation and Survival by Modulating Nuclear Import

Choo¹,

Cutler

Rother

et al. 2016

Stem Cells

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Satellite cells are stem cells with an essential role in skeletal muscle repair. Precise regulation of gene expression is critical for proper satellite cell quiescence, proliferation, differentiation and self -renewal. Nuclear proteins required for gene expression are dependent on the nucleocytoplasmic transport machinery to access to nucleus, however little is known about regulation of nuclear transport in satellite cells. The best characterized nuclear import pathway is classical nuclear import which depends on a classical nuclear localization signal (cNLS) in a cargo protein and the heterodimeric import receptors, karyopherin alpha (KPNA) and beta (KPNB). Multiple KPNA1 paralogs exist and can differ in importing specific cNLS proteins required for cell differentiation and function. We show that transcripts for six Kpna paralogs underwent distinct changes in mouse satellite cells during muscle regeneration accompanied by changes in cNLS proteins in nuclei. Depletion of KPNA1, the most dramatically altered KPNA, caused satellite cells in uninjured muscle to prematurely activate, proliferate and undergo apoptosis leading to satellite cell exhaustion with age. Increased proliferation of satellite cells led to enhanced muscle regeneration at early stages of regeneration. In addition, we observed impaired nuclear localization of two key KPNA1 cargo proteins: p27, a cyclin-dependent kinase inhibitor associated with cell cycle control and lymphoid enhancer factor 1, a critical co-transcription factor for β-catenin. These results indicate that regulated nuclear import of proteins by KPNA1 is critical for satellite cell proliferation and survival and establish classical nuclear import as a novel regulatory mechanism for controlling satellite cell fate.

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“…When needed, the open source websites "STRING" [89] and Wiki-Pi [90] were used to perform meta-analyses of protein-protein interactions. STRING allows protein interaction networks to be generated via a survey of distinct databases that list known protein interactions from published and manually-curated biochemical studies [89].…”

Section: Meta-analysis Of Mycn Protein Interactantsmentioning

confidence: 99%

A Unique TGFB1-Driven Genomic Program Links Astrocytosis, Low-Grade Inflammation and Partial Demyelination in Periplaques of Spinal Cords from Progressive Multiple Sclerosis Patients

Nataf¹,

Barritault²,

Pays³

2017

Preprint

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Abstract:We previously reported that in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses comparing periplaques to adjacent normal-appearing white matter (NAWM) areas did not allow providing a comprehensive view of molecular events in astrocytes vs oligodendrocytes. Here, we re-assessed our transcriptomic data with the aim of identifying functionally-relevant co-expression networks that would reflect astrocyte vs oligodendrocyte molecular signatures in periplaques. We identified an astrocytosis-related gene module comprising GFAP, the hub gene CX43/GJA1 and a set of transcripts forming a TGFB/SMAD1/SMAD2 genomic signature. Partial demyelination was characterized by a co-expression network which, besides myelin genes, comprised a highly significant number of translation/elongation-related genes. Interestingly, the main oligodendrocyte-related hub we identified was NDRG1, a gene previously shown to be specifically silenced in the NAWM of MS patients. This result indicated that NDRG1 down-regulation could be an important event in the process of periplaque partial demyelination. To establish a putative link between NDRG1 down-regulation and a cytokine/chemokine signature, we then sought to identify cytokine/chemokine genes whose mRNA levels inversely correlated with those of NDRG1. Following this approach we found 5 candidate immune-related genes whose up-regulation associated with NDRG1 down-regulation: TGFB1, PDGFC, . From these results we propose that in the spinal cord of MS patients with progressive forms of the disease, TGFB1 may Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

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Wiki-Pi: A Web-Server of Annotated Human Protein-Protein Interactions to Aid in Discovery of Protein Function

Cited by 75 publications

References 39 publications

Analysis of chromatin-state plasticity identifies cell-type–specific regulators of H3K27me3 patterns

Analysis of chromatin-state plasticity identifies cell-type–specific regulators of H3K27me3 patterns

Karyopherin Alpha 1 Regulates Satellite Cell Proliferation and Survival by Modulating Nuclear Import

A Unique TGFB1-Driven Genomic Program Links Astrocytosis, Low-Grade Inflammation and Partial Demyelination in Periplaques of Spinal Cords from Progressive Multiple Sclerosis Patients

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