Retinoic acid and methylation cis-regulatory elements control the mouse tissue non-specific alkaline phosphatase gene expression

D. Escalante-Alcalde, F. Recillas-Targa, D. Hernández-García, S. Castro-Obregón, M. Terao, E. Garattini, L. Covarrubias

Research output: Contribution to journalArticle

Abstract

To understand the mechanisms regulating the tissue non-specific alkaline phosphatase (TNAP) activity during development, we characterized cis-transcriptional regulatory elements. In embryonic cells and tissues, TNAP expression was driven preferentially by the exon 1A (E1A) promoter, one of the two promoters previously defined. Transcriptional activity of E1A promoter was up-regulated by retinoic acid (RA) through a putative RA-responsive element. Transgenic mice analysis with lacZ reporter constructs revealed negative regulatory elements within 8.5 kb of E1A promoter. Promoter sequences of endogenous TNAP in non-expressing tissues and those carried by the 8.5 kb-lacZ transgene were found to be highly methylated. A 1 kb fragment of E1A promoter increased the methylation level of lacZ and promoter sequences. The role of RA and DNA methylation in defining the embryonic expression pattern of TNAP is discussed.

Original languageEnglish
Pages (from-to)21-32
Number of pages12
JournalMechanisms of Development
Volume57
Issue number1
DOIs
Publication statusPublished - Jun 1996

Keywords

  • Alkaline phosphatase
  • Methylation
  • Mouse development
  • Primordial germ cells
  • Promoter
  • Retinoic acid

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

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