Transcription Factor CTIP1/ BCL11A Regulates Epidermal Differentiation and Lipid Metabolism During Skin Development

Sci Rep. 2017 Oct 18;7(1):13427. doi: 10.1038/s41598-017-13347-7.


The epidermal permeability barrier (EPB) prevents organisms from dehydration and infection. The transcriptional regulation of EPB development is poorly understood. We demonstrate here that transcription factor COUP-TF-interacting protein 1 (CTIP1/BCL11A; hereafter CTIP1) is highly expressed in the developing murine epidermis. Germline deletion of Ctip1 (Ctip1 -/-) results in EPB defects accompanied by compromised epidermal differentiation, drastic reduction in profilaggrin processing, reduced lamellar bodies in granular layers and significantly altered lipid composition. Transcriptional profiling of Ctip1 -/- embryonic skin identified altered expression of genes encoding lipid-metabolism enzymes, skin barrier-associated transcription factors and junctional proteins. CTIP1 was observed to interact with genomic elements within the regulatory region of the gene encoding the differentiation-associated gene, Fos-related antigen2 (Fosl2) and lipid-metabolism-related gene, Fatty acid elongase 4 (Elvol4), and the expression of both was altered in Ctip1 -/- mice. CTIP1 appears to play a role in EPB establishment of via direct or indirect regulation of a subset of genes encoding proteins involved in epidermal differentiation and lipid metabolism. These results identify potential, CTIP1-regulated avenues for treatment of skin disorders involving EBP defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation*
  • DNA-Binding Proteins
  • Epidermal Cells / cytology
  • Epidermal Cells / metabolism*
  • Fatty Acid Elongases
  • Fos-Related Antigen-2 / genetics
  • Fos-Related Antigen-2 / metabolism
  • Gene Expression Regulation, Developmental
  • Lipid Metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Repressor Proteins
  • Skin / embryology*


  • Bcl11a protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Fos-Related Antigen-2
  • Fosl2 protein, mouse
  • Nuclear Proteins
  • Repressor Proteins
  • Acetyltransferases
  • Fatty Acid Elongases