The functional diversity of Drosophila Ino80 in development

Ghasemi, Mohsen; Pawar, Hema; Mishra, Rakesh; Brahmachari, Vani

doi:10.1016/j.mod.2015.07.014

Cited by 5 publications

(25 citation statements)

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“…Therefore, it was interesting to test if this chromatin remodelling protein has trithorax like function in regulating developmental genes including the homeotic genes. We have carried out the validation of the role of dIno80, the Drosophila homologue, in developmental gene regulation . As we have earlier reported, dIno80 regulates homeotic genes and interacts with both activating complex, the Trithorax complex as well as the repressive complex, the Polycomb complex.…”

Section: Resultsmentioning

confidence: 88%

“…As we have earlier reported, dIno80 regulates homeotic genes and interacts with both activating complex, the Trithorax complex as well as the repressive complex, the Polycomb complex. In Drosophila several proteins of similar dual function are known and these have been designated as Enhancers of Trithorax and Polycomb proteins (ETP) …”

Section: Resultsmentioning

confidence: 99%

“…Based on the homology search hIno80 (INOC1, OMIM Accession no.610169) protein was identified in the human genome . The results of our work on signature peptide identification for developmental function, led to us to predict and subsequently validate the function of Ino80 in development . The above in silico analysis facilitates the identification of such invariant peptide motifs in ATPases of different classes.…”

Section: Resultsmentioning

confidence: 99%

“…In Drosophila several proteins of similar dual function are known and these have been designated as Enhancers of Trithorax and Polycomb proteins (ETP). [28][29][30] Because dIno80 interacts with both Polycomb and Trithorax complexes, we searched for additional signatures shared between dIno80 and the other members of PcG and trxG from the Drosophila using the L-HOST programme. The protein sequences of Ino80 and all the known members of the Polycomb and Trithorax family which had the 14mer motif were retrieved from the NCBI database.…”

Section: Figurementioning

confidence: 99%

“…10,26 The results of our work on signature peptide identification for developmental function, led to us to predict and subsequently validate the function of Ino80 in development. 28,29 The above in silico analysis facilitates the identification of such invariant peptide motifs in ATPases of different classes. The motifs identified for ATPases map to many uncharacterized proteins.…”

Section: Figurementioning

confidence: 99%

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Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

et al. 2017

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The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

et al. 2017

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The regulatory function of dIno80 correlates with its DNA binding activity

Jain

Maini

Narang

et al. 2020

Gene

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The INO80 complex, including the Ino80 protein, forms a highly conserved canonical complex that remodels chromatin in the context of multiple cellular functions. The Drosophila homologue, dIno80, is involved in homeotic gene regulation during development as a canonical Pho-dIno80 complex. Previously, we found that dIno80 regulates homeotic genes by interacting with epigenetic regulators, such as polycomb and trithorax, suggesting the occurrence of non-canonical Ino80 complexes. Here using spectroscopic methods and gel retardation assays, we identified a set of consensus DNA sequences that DNA binding domain of dIno80 (DBINO) interacts with having differential affinity and high specificity. Testing these sequences in reporter assays, showed that this interaction can positively regulate transcription. These results suggest that, dIno80 has a sequence preference for interaction with DNA leading to transcriptional changes. SIGNIFICANCEThe chromatin remodeling proteins control gene expression by nucleosome sliding and exchange. They are known to function as multi-subunit complexes recruited to chromatin by transcription factors or histone modification readers. Here, we report a sequence specific binding potential for the chromatin remodeler, dIno80. We have carried out in vitro studies with DNA binding domain of dIno80 to elucidate its sequence specific DNA binding. We have also showed that this binding can regulated reporter gene expression in Drosophila cells. Our results suggest a non-canonical role of Ino80 in transcriptional regulation.

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The regulatory function of dIno80 correlates with its DNA binding activity

Jain

Maini

Narang

et al. 2019

Preprint

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Running title: DNA binding activity of dIno80 Abbreviations: dIno80, Drosophila Ino80; hIno80; human Ino80; Ino80, Inositol requiring mutant 80; ETP, Enhancer of Trithorax and Polycomb; FID, fluorescence intercalator displacement; DBINO, DNA binding domain of Ino80; EMSA, electrophoretic mobility shift assay. Highlights  dIno80 has a DNA binding domain through which it recognizes a consensus sequence and interacts with DNA.  dIno80 interacts with variants of the consensus sequence with variable affinity.  dIno80 can regulate the expression of downstream as well as upstream reporter gene.  dIno80 can complement the function of Pho and rescue Pho lethality. 2 ABSTRACTThe INO80 complex, including the Ino80 protein, forms a highly conserved canonical complex that remodels chromatin in the context of multiple cellular functions. The Drosophila homologue, dIno80, is involved in homeotic gene regulation during development as a canonical Pho-dIno80 complex. Previously, we found that dIno80 regulates homeotic genes by interacting with epigenetic regulators, such as polycomb and trithorax, suggesting the occurrence of non-canonical Ino80 complexes. Here using spectroscopic methods and gel retardation assays, we identified a set of consensus DNA sequences that DNA binding domain of dIno80 (DBINO)interacts with havingdifferential affinity and high specificity. Testing these sequences in reporters showed that this interaction can positively regulate transcription. We also demonstrated that over-expressing dIno80 can rescue the pupal lethality of pleiohomeotic (pho) deficient flies. These results suggest that, in addition to its known function as a chromatin remodeler, dIno80 has sequence preference for interaction with DNA to regulate transcription.

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The functional diversity of Drosophila Ino80 in development

Cited by 5 publications

References 50 publications

Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

The regulatory function of dIno80 correlates with its DNA binding activity

The regulatory function of dIno80 correlates with its DNA binding activity

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