[Expression and Regulation of Tal2 during Neuronal Differentiation in P19 Cells]

Yakugaku Zasshi. 2017;137(1):61-71. doi: 10.1248/yakushi.16-00176.
[Article in Japanese]

Abstract

T-cell acute lymphocytic leukemia 2 (Tal2) is a gene encoding a member of the basic helix-loop-helix transcription factor family, which is essential for the normal development of the mouse brain. We found that Tal2 was induced during neural differentiation in P19 cells, which are pluripotent mouse embryonal carcinoma cells that differentiate into the neural lineage upon both exposure to all-trans retinoic acid (atRA) and the formation of cell aggregation. Tal2 expression during neural differentiation in P19 cells was detected within 3 h after induction with atRA and retinoic acid receptor α (RARα). The atRA-RARα complex is known to bind to a characteristic retinoic acid response element (RARE) located in the promoter of target genes. We found a RARE-like element in the intron of Tal2. We also found a TATA-box-like element in the 5' region. The TATA-box-like element functioned as a core promoter, and TATA- box binding protein bound to this element upstream of Tal2 in P19 cells. The RARE-like element responded to atRA signaling that activated the transcription, and RARα was bound to this element in the intron of Tal2 in P19 cells. Furthermore, the interaction between these elements on Tal2 was confirmed in a chromatin immunoprecipitation assay. Because the neural differentiation of P19 cells mimics in part the development of the nervous system, P19 cells are useful for studying the mechanism underlying the role of Tal2 in neural differentiation. Further work is underway to clarify the function of Tal2 in neural differentiation using the differentiation system of P19 cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Differentiation / genetics*
  • Gene Expression / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Mice
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology*
  • Neurons / cytology*
  • Promoter Regions, Genetic
  • Retinoic Acid Receptor alpha
  • TATA Box
  • Tretinoin / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Neoplasm Proteins
  • Retinoic Acid Receptor alpha
  • Tal2 protein, mouse
  • Tretinoin