Alterations in the Sp1 binding and Fmr-1 gene expression in the cortex of the brain during maturation and aging of mouse

Mol Biol Rep. 2014 Oct;41(10):6855-63. doi: 10.1007/s11033-014-3571-1. Epub 2014 Jul 12.

Abstract

Fragile X mental retardation protein (FMRP) has been implicated in learning, memory and cognition, therefore, information on alterations in FMRP expression during maturation and aging may provide a clue towards understanding mechanisms of age-dependent cognitive changes in the brain. In the present paper, we have studied Fmr-1 gene expression and its correlation with interaction of a tans-acting factor Sp1with Fmr-1 promoter in the cerebral cortex of female mice at post natal period during maturation and aging. Our data reveal that level of Fmr-1 transcript in the cerebral cortex is significantly up regulated at day 7 after birth compared to day 0 (the day of birth) and is gradually down regulated from day 15 onward to old age. The pattern of Fmr-1 transcript levels corresponds with the level of FMRP, however, its level is significantly up regulated in old age compared to adult mice. Our EMSA data revealed the formation of a single complex as a result of binding of Sp1with Fmr-1 promoter sequence. Its intensity gradually decreased from the day 0 (day of birth) till day 15, remained unaltered in young, significantly decreased in adult and significantly increased in old age. Our data suggests that age-dependent alteration in the Fmr-1 gene expression is associated with Sp1 interaction with Fmr-1 promoter which in turn might be related with cognitive development during brain maturation and aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / genetics
  • Animals
  • Cerebral Cortex / metabolism*
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Mental Retardation Protein / metabolism
  • Gene Expression Regulation*
  • Mice
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms
  • RNA, Messenger / genetics
  • Sp1 Transcription Factor / metabolism*
  • Transcription, Genetic

Substances

  • Fmr1 protein, mouse
  • Protein Isoforms
  • RNA, Messenger
  • Sp1 Transcription Factor
  • Fragile X Mental Retardation Protein