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Identification of Transcriptional Regulators of Psoriasis from RNA-Seq Experiments

  • Alena Zolotarenko
  • Evgeny Chekalin
  • Rohini Mehta
  • Ancha Baranova
  • Tatiana V. Tatarinova
  • Sergey BruskinEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1613)

Abstract

Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the molecular mechanisms of regulation of the disease we performed RNA sequencing (RNA-Seq) analysis of 14 pairs of skin samples collected from psoriatic patients. Subsequent pathway analysis and an extraction of transcriptional regulators governing psoriasis-associated pathways was executed using a combination of MetaCore Interactome enrichment tool and cisExpress algorithm, and followed by comparison to a set of previously described psoriasis response elements. A comparative approach has allowed us to identify 42 core transcriptional regulators of the disease associated with inflammation (NFkB, IRF9, JUN, FOS, SRF), activity of T-cells in the psoriatic lesions (STAT6, FOXP3, NFATC2, GATA3, TCF7, RUNX1, etc.), hyperproliferation and migration of keratinocytes (JUN, FOS, NFIB, TFAP2A, TFAP2C), and lipid metabolism (TFAP2, RARA, VDR). After merging the ChIP-seq and RNA-seq data, we conclude that the atypical expression of FOXA1 transcriptional factor is an important player in psoriasis, as it inhibits maturation of naive T cells into this Treg subpopulation (CD4+FOXA1+CD47+CD69+PD-L1(hi)FOXP3−), therefore contributing to the development of psoriatic skin lesions.

Key words

Psoriasis RNA-Seq FOXA1 Transcriptional regulation Inflammation Signaling pathways 

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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Alena Zolotarenko
    • 1
  • Evgeny Chekalin
    • 1
  • Rohini Mehta
    • 2
  • Ancha Baranova
    • 2
    • 3
    • 4
    • 5
  • Tatiana V. Tatarinova
    • 5
    • 6
    • 7
  • Sergey Bruskin
    • 1
    • 4
    Email author
  1. 1.Laboratory of Functional GenomicsVavilov Institute of General Genetics RASMoscowRussia
  2. 2.The Center of the Study of Chronic Metabolic and Rare Diseases, School of Systems BiologyGeorge Mason UniversityFairfaxUSA
  3. 3.Research Centre for Medical Genetics RAMSMoscowRussia
  4. 4.Moscow Institute of Physics and TechnologyMoscowRussia
  5. 5.Atlas Biomed GroupMoscowRussia
  6. 6.Center for Personalized Medicine, Children’s Hospital Los Angeles and Spatial Sciences InstituteUniversity of Southern CaliforniaLos AngelesUSA
  7. 7.A.A. Kharkevich Institute for Information Transmission Problems RASMoscowRussia

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