JCB logo
BD Biosciences
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online December 3, 2007
doi:10.1083/jcb.200708086
The Journal of Cell Biology, Vol. 179, No. 5, 825-832
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Wright et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1537K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Related biobytes podcast
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wright, K. M.
Right arrow Articles by Deshmukh, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wright, K. M.
Right arrow Articles by Deshmukh, M.
Related Collections
Right arrowRelated In this Issue article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Report

 Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature neurons

Kevin M. Wright1, Michelle I. Smith1,2, Lila Farrag1, and Mohanish Deshmukh1,2

1 Neuroscience Center and 2 Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

Correspondence to M. Deshmukh: mohanish{at}med.unc.edu

Although apoptosis has been extensively studied in developing neurons, the dynamic changes in this pathway after neuronal maturation remain largely unexplored. We show that as neurons mature, cytochrome c– mediated apoptosis progresses from inhibitor of apoptosis protein–dependent to –independent regulation because of a complete loss of Apaf-1 expression. However, after DNA damage, mature neurons resynthesize Apaf-1 through the cell cycle–related E2F1 pathway and restore their apoptotic potential. Surprisingly, we find that E2F1 is sufficient to induce Apaf-1 expression in developing but not mature neurons. Rather, Apaf-1 up-regulation in mature neurons requires both chromatin derepression and E2F1 transcriptional activity. This differential capacity of E2F1 to induce Apaf-1 transcription is because of the association of the Apaf-1 promoter with active chromatin in developing neurons and repressed chromatin in mature neurons. These data specifically illustrate how the apoptotic pathway in mature neurons becomes increasingly restricted by a novel mechanism involving the regulation of chromatin structure.

K.M. Wright and M.I. Smith contributed equally to this paper.

Abbreviations used in this paper: AcH3, acetylated histone 3; ChIP, chromatin immunoprecipitation; HDAC, histone deacetylase; IAP, inhibitor of apoptosis protein; MeH3K9, histone 3 trimethylated on lysine 9; P, postnatal day; Smac, second mitochondria-derived activator of caspases; TSA, trichostatin A; XIAP, X-linked IAP.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related In this Issue article

Apoptotic inaccessibility with maturity
Nicole LeBrasseur
J. Cell Biol. 2007 179: 806. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents