Skip to main content

Following Transcriptome to Uncover FOXO Biological Functions

  • Protocol
  • First Online:
FOXO Transcription Factors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1890))

Abstract

Two and half million red blood cells (RBC) are generated every second in a healthy adult. The process of RBC production known as erythropoiesis requires a meticulous synchrony between signaling processes and the activity of many transcription factor complexes. FOXO3 is a transcription factor that is responsive to signaling processes and essential for the erythroid proliferation and maturation, RBC formation, and lifespan. Here, we discuss how using an integrated computational and experimental systems biology approach new and unanticipated FOXO3 functions in terminal erythropoiesis were uncovered. These combinatory approaches identified FOXO3 as a key regulator of terminal erythropoiesis. As a result, a new mode of FOXO3 participation in erythroid transcription complex formation has been proposed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kerenyi MA, Orkin SH (2010) Networking erythropoiesis. J Exp Med 207:2537–2541

    Article  CAS  Google Scholar 

  2. Ferreira R, Ohneda K, Yamamoto M, Philipsen S (2005) GATA1 function, a paradigm for transcription factors in hematopoiesis. Mol Cell Biol 25:1215–1227

    Article  CAS  Google Scholar 

  3. Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, Regan M, Weatherall D, Chou DP, Eisele TP, Flaxman SR, Pullan RL, Brooker SJ, Murray CJ (2014) A systematic analysis of global anemia burden from 1990 to 2010. Blood 123:615–624

    Article  CAS  Google Scholar 

  4. Goodman SB, Block MH (1967) Increased red blood cell production in chronic myelocytic leukemia. JAMA 200:621–624

    Article  CAS  Google Scholar 

  5. Salih DA, Brunet A (2008) FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 20:126–136

    Article  CAS  Google Scholar 

  6. Eijkelenboom A, Burgering BM (2013) FOXOs: signalling integrators for homeostasis maintenance. Nat Rev Mol Cell Biol 14:83–97

    Article  CAS  Google Scholar 

  7. Bakker WJ, Blazquez-Domingo M, Kolbus A, Besooyen J, Steinlein P, Beug H, Coffer PJ, Lowenberg B, von Lindern M, van Dijk TB (2004) FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1. J Cell Biol 164:175–184

    Article  CAS  Google Scholar 

  8. Bakker WJ, van Dijk TB, Parren-van Amelsvoort M, Kolbus A, Yamamoto K, Steinlein P, Verhaak RG, Mak TW, Beug H, Lowenberg B, von Lindern M (2007) Differential regulation of Foxo3a target genes in erythropoiesis. Mol Cell Biol 27:3839–3854

    Article  CAS  Google Scholar 

  9. Ghaffari S, Jagani Z, Kitidis C, Lodish HF, Khosravi-Far R (2003) Cytokines and BCR-ABL mediate suppression of TRAIL-induced apoptosis through inhibition of forkhead FOXO3a transcription factor. Proc Natl Acad Sci U S A 100:6523–6528

    Article  CAS  Google Scholar 

  10. Kashii Y, Uchida M, Kirito K, Tanaka M, Nishijima K, Toshima M, Ando T, Koizumi K, Endoh T, Sawada K, Momoi M, Miura Y, Ozawa K, Komatsu N (2000) A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction. Blood 96:941–949

    Article  CAS  Google Scholar 

  11. Marinkovic D, Zhang X, Yalcin S, Luciano JP, Brugnara C, Huber T, Ghaffari S (2007) Foxo3 is required for the regulation of oxidative stress in erythropoiesis. J Clin Invest 117:2133–2144

    Article  CAS  Google Scholar 

  12. Liang R, Camprecios G, Kou Y, McGrath K, Nowak R, Catherman S, Bigarella CL, Rimmele P, Zhang X, Gnanapragasam MN, Bieker JJ, Papatsenko D, Ma'ayan A, Bresnick E, Fowler V, Palis J, Ghaffari S (2015) A systems approach identifies essential FOXO3 functions at key steps of terminal erythropoiesis. PLoS Genet 11:e1005526

    Article  Google Scholar 

  13. Franco SS, De Falco L, Ghaffari S, Brugnara C, Sinclair DA, Matte A, Iolascon A, Mohandas N, Bertoldi M, An X, Siciliano A, Rimmele P, Cappellini MD, Michan S, Zoratti E, Anne J, De Franceschi L (2014) Resveratrol accelerates erythroid maturation by activation of FoxO3 and ameliorates anemia in beta-thalassemic mice. Haematologica 99:267–275

    Article  CAS  Google Scholar 

  14. Yu D, dos Santos CO, Zhao G, Jiang J, Amigo JD, Khandros E, Dore LC, Yao Y, D'Souza J, Zhang Z, Ghaffari S, Choi J, Friend S, Tong W, Orange JS, Paw BH, Weiss MJ (2010) miR-451 protects against erythroid oxidant stress by repressing 14-3-3zeta. Genes Dev 24:1620–1633

    Article  CAS  Google Scholar 

  15. McIver SC, Kang YA, DeVilbiss AW, O’Driscoll CA, Ouellette JN, Pope NJ, Camprecios G, Chang CJ, Yang D, Bouhassira EE, Ghaffari S, Bresnick EH (2014) The exosome complex establishes a barricade to erythroid maturation. Blood 124:2285–2297

    Article  CAS  Google Scholar 

  16. Zhang X, Camprecios G, Rimmele P, Liang R, Yalcin S, Mungamuri SK, Barminko J, D’Escamard V, Baron MH, Brugnara C, Papatsenko D, Rivella S, Ghaffari S (2014) FOXO3-mTOR metabolic cooperation in the regulation of erythroid cell maturation and homeostasis. Am J Hematol 89:954–963

    Article  CAS  Google Scholar 

  17. Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR, Ma’ayan A (2010) ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26:2438–2444

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work in the Ghaffari lab is supported by grants from National Institutes of Health (NCI and NHLBI). Raymond Liang is supported by a pre-doctoral fellowship from the American Heart Association.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Saghi Ghaffari .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Liang, R., Menon, V., Ghaffari, S. (2019). Following Transcriptome to Uncover FOXO Biological Functions. In: Link, W. (eds) FOXO Transcription Factors. Methods in Molecular Biology, vol 1890. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-8900-3_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8900-3_18

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-8899-0

  • Online ISBN: 978-1-4939-8900-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics