Cathepsin L Proteolytically Processes Histone H3 During Mouse Embryonic Stem Cell Differentiation

Elizabeth M. Duncan, Tara L. Muratore-Schroeder, Richard G. Cook, Benjamin A. Garcia, Jeffrey Shabanowitz, Donald F. Hunt, C. David Allis

Research output: Contribution to journalArticlepeer-review

262 Scopus citations

Abstract

Chromatin undergoes developmentally-regulated structural and chemical changes as cells differentiate, which subsequently lead to differences in cellular function by altering patterns of gene expression. To gain insight into chromatin alterations that occur during mammalian differentiation, we turned to a mouse embryonic stem cell (ESC) model. Here we show that histone H3 is proteolytically cleaved at its N-terminus during ESC differentiation. We map the sites of H3 cleavage and identify Cathepsin L as a protease responsible for proteolytically processing the N-terminal H3 tail. In addition, our data suggest that H3 cleavage may be regulated by covalent modifications present on the histone tail itself. Our studies underscore the intriguing possibility that histone proteolysis, brought about by Cathepsin L and potentially other family members, plays a role in development and differentiation that was not previously recognized.

Original languageEnglish
Pages (from-to)284-294
Number of pages11
JournalCell
Volume135
Issue number2
DOIs
StatePublished - Oct 17 2008

Bibliographical note

Funding Information:
We thank J. Wysocka, T. Swigut, A. Ruthenburg, D. Shechter, L, Banaszynski, and B. Ueberheide for their advice on biochemical and ESC methods, and J. Wysocka and D. Shechter for their critical reading of the manuscript. Peptides were synthesized at the proteomics facilities at RU and Tufts. E.M.D. is an Anderson Cancer Center fellow (The Rockefeller University). This work was funded by institutional support from The Rockefeller University and grants from the Tri-Institutional Stem Cell Initiative (funded by the Starr Foundation) and National Institutes of Health Grants GM37537 (to D.F.H.) and GM53512 (to C.D.A.).

Keywords

  • DNA
  • PROTEINS
  • STEMCELL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)

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