Functional role of Bap170 domains in enhancer-dependent gene activity in Drosophila Melanogaster

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Abstract

The Bap170 subunit of the SWI/SNF chromatin remodeler exhibits activator functions when artificially recruited to the LacZ reporter promoter in enhancer-dependent transcription. In this study, the functional significance of Bap170 protein domains in reporter activation was analyzed. Deletion of the ARID domain does not reduce Bap170 activity. Increased expression of the LacZ reporter was observed in the form of Bap170 without a region that includes LXXLL motifs. Deletions of the central (RFX domain and IDRs) and C-terminal region (zinc fingers) lead to a significant decrease in transgene expression. Apparently, these regions of Bap170 are critical for the function of this protein in activated transcription.

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About the authors

V. K. Chmykhalo

Institute of Gene Biology, Russian Academy of Sciences

Author for correspondence.
Email: vkchmykhalo@icloud.com

Laboratory of Gene Expression Regulation in Development

Russian Federation, Moscow

D. Amendola

Università di Napoli Federico II

Email: vkchmykhalo@icloud.com
Italy, Naples

Y. V. Shidlovskii

Institute of Gene Biology, Russian Academy of Sciences

Email: vkchmykhalo@icloud.com

Laboratory of Gene Expression Regulation in Development

Russian Federation, Moscow

L. A. Lebedeva

Institute of Gene Biology, Russian Academy of Sciences

Email: vkchmykhalo@icloud.com

Laboratory of Gene Expression Regulation in Development

Russian Federation, Moscow

P. Schedl

Princeton University

Email: vkchmykhalo@icloud.com

foreign member of RAS

United States, Princeton

E Giordano

Università di Napoli Federico II

Email: vkchmykhalo@icloud.com
Italy, Naples

References

  1. Reyes, A.A., R.D. Marcum, and Y. He. Structure and Function of Chromatin Remodelers // J Mol Biol. 2021. 433(14). Р. 166929.
  2. Singh, A., et al. SWI/SNF Chromatin Remodelers: Structural, Functional and Mechanistic Implications // Cell Biochem Biophys. 2023. 81(2). Р. 167–187.
  3. Hernández-García, J., et al. Comprehensive identification of SWI/SNF complex subunits underpins deep eukaryotic ancestry and reveals new plant components // Communications Biology. 2022. 5(1). Р. 549.
  4. Chmykhalo, V.K., et al. SWI/SNF Complex Connects Signaling and Epigenetic State in Cells of Nervous System // Mol Neurobiol. 2024.
  5. Chmykhalo, V.K., et al. Effects of Overexpression of Specific Subunits SAYP, Bap170 of the Chromatin Remodeling Complex in Drosophila Melanogaster // Doklady Biochemistry and Biophysics. 2024.
  6. Vorobyeva, N.E., et al. SAYP and Brahma are important for ‘repressive’ and ‘transient’ Pol II pausing // Nucleic Acids Res. 2012. 40(15). Р. 7319–31.
  7. Moshkin, Y.M., et al. Remodelers Organize Cellular Chromatin by Counteracting Intrinsic Histone-DNA Sequence Preferences in a Class-Specific Manner // Molecular and Cellular Biology. 2012. 32(3). Р. 675–688.
  8. Vorobyeva, N.E., et al. Transcription coactivator SAYP combines chromatin remodeler Brahma and transcription initiation factor TFIID into a single supercomplex // Proc Natl Acad Sci U S A. 2009. 106(27). Р. 11049–54.
  9. Panov, V.V., et al. Transcription co-activator SAYP mediates the action of STAT activator // Nucleic Acids Res. 2012. 40(6). Р. 2445–53.
  10. Carrera, I., J. Zavadil, and J.E. Treisman. Two subunits specific to the PBAP chromatin remodeling complex have distinct and redundant functions during drosophila development // Mol Cell Biol. 2008. 28(17). Р. 5238–50.
  11. Rendina, R., et al. Bap170, a subunit of the Drosophila PBAP chromatin remodeling complex, negatively regulates the EGFR signaling // Genetics. 2010. 186(1). Р. 167–81.
  12. Carcamo, S., et al. Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma // Cell Reports. 2022. 39(1). Р. 110637.
  13. Soshnikova, N.V., et al. A novel chromatin-remodeling complex variant, dcPBAF, is involved in maintaining transcription in differentiated neurons // Front Cell Dev Biol. 2023. 11. Р. 1271598.
  14. Li, M., et al. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma // Nat Genet. 2011. 43(9). Р. 828–9.
  15. Akinjiyan, F.A., et al. ARID2 mutations may relay a distinct subset of cutaneous melanoma patients with different outcomes // Sci Rep. 2024. 14(1). Р. 3444.
  16. Shidlovskii, Y.V., et al. Subunits of the PBAP Chromatin Remodeler Are Capable of Mediating Enhancer-Driven Transcription in Drosophila // Int J Mol Sci. 2021. 22(6).
  17. Plevin, M.J., M.M. Mills, and M. Ikura. The LxxLL motif: a multifunctional binding sequence in transcriptional regulation // Trends Biochem Sci. 2005. 30(2). Р. 66–9.
  18. Bramswig, N.C., et al. Heterozygosity for ARID2 lossof- function mutations in individuals with a Coffin-Siris syndrome-like phenotype // Hum Genet. 2017. 136(3). Р. 297–305.

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2. Fig. 1. Structure of the Bap170 protein and its mutant forms. a – Domain structure of Bap170. The regions deleted in the analyzed mutants are indicated. The numbers of amino acid residues at the boundaries of the regions are given. b – Scheme of the used model of the enhancer-dependent transgene LexAop::LacZ, expressed under the control of the fusion protein LexA-Bap170. c – The genetic constructs used and the mutant forms of Bap170 encoded by them.

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3. Fig. 2. Activity of Bap170 deletion variants in enhancer-dependent expression of the LacZ transgene in the antennal and wing imaginal discs of 3rd instar larvae. The exposure during staining is the same for all lines. wt – in this case LexA-Bap170. The enhancer localized near the insertion of the lacZ transgene is indicated on the left.

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