Aging and non-sirtuin histone modifications

Chapter

Abstract

  • © Springer Science+Business Media, LLC 2010. All rights reserved. Histones, once thought of as static structural elements, are now known to be dynamic and integral elements of the machinery responsible for regulating gene transcription. Modification of histones and/or DNA can alter the strength of their association and thus, together, modulate transcriptional activity. Acetylation of histones neutralizes their positively charged, lysine-rich amino-terminal tails, loosening the histone-DNA contacts, thus making DNA more accessible at these specific sites for transcription. It is widely accepted that there is a direct correlation between histone acetylation and transcriptional activity for a given segment of chromatin. Histone acetyltransferases (HATs) facilitate histone acetylation and are thus believed to act as transcriptional activators. In contrast, histone deacetylases (HDACs) remove acetyl groups from histones and thereby repress transcription by compacting DNA. The balance between the activity of HATs and HDACs regulates transcription, but with aging this balance is lost, leading to either gene overactivity (e.g., in cancer cells) or gene repression that can lead to neurodegeneration during the aging process.
  • Authors

    Digital Object Identifier (doi)

    International Standard Book Number (isbn) 13

  • 9781441906380
  • Start Page

  • 41
  • End Page

  • 50