Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Liver x receptor-retinoid x receptor (lxr-rxr) heterodimer cistrome reveals coordination of lxr and ap1 signaling in keratinocytes

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Shen, Q.
  • Bai, Y. C.
  • Chang, K. C. N.
  • Wang, Y. J.
  • Burris, Thomas
  • Freedman, L. P.
  • Thompson, C. C.
  • Nagpal, S.

publication date

  • April 2011

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Liver X receptors (LXRs) play a critical role in regulating lipid synthesis and transport in numerous tissues. In the skin, activation of LXR induces keratinocyte differentiation and improves epidermal permeability barrier homeostasis. To elucidate the mechanism of LXR action in skin, we mapped its cistrome by identifying LXRβ-RXRα binding sites using ChIP-on-chip in normal human epidermal keratinocytes (NHEKs). The cistrome was integrated with transcription data to obtain a global view of LXR action in keratinocyte biology. Here, we identify 2035 LXRβ-RXRα binding sites containing 4794 LXR response elements in NHEKs and show the presence of consensus heterodimer active regions in genes involved in keratinocyte lipid transport/synthesis and terminal differentiation. Bioinformatics analysis of the cistrome revealed an enrichment of AP1 cis-regulatory motifs in the vicinity of the LXRβ-RXRα binding sites. Importantly, we have demonstrated a direct interaction between LXR and Jun/Fos, indicating that the cooperation between LXR and AP1 may orchestrate keratinocyte differentiation. Finally, we corroborated these results by genome-wide mapping of the c-Fos and c-Jun cistromes in NHEKs, demonstrating that 77% of all the LXRβ-RXRα binding regions show the presence of AP1 motifs at adjacent locations. Our findings provide new insight into the mechanism of LXR action in keratinocyte differentiation, lipid production and barrier formation, further strengthening the validation of LXR as a potential therapeutic target for skin disorders including skin aging, psoriasis, and atopic dermatitis.

subject areas

  • Animals
  • Binding Sites
  • Cell Differentiation
  • Dimerization
  • Gene Expression Regulation
  • Genome
  • Humans
  • Keratinocytes
  • Mice
  • Mice, Knockout
  • Orphan Nuclear Receptors
  • Retinoid X Receptors
  • Signal Transduction
  • Skin
  • Transcription Factor AP-1
scroll to property group menus

Identity

PubMed Central ID

  • PMC3077653

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M110.165704

PubMed ID

  • 21349840
scroll to property group menus

Additional Document Info

start page

  • 14554

end page

  • 14563

volume

  • 286

issue

  • 16

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support