Histone posttranslational modifications and cell fate determination: Lens induction requires the lysine acetyltransferases CBP and p300

Louise Wolf, Wilbur Harrison, Jie Huang, Qing Xie, Ningna Xiao, Jian Sun, Lingkun Kong, Salil A. Lachke, Murali R. Kuracha, Venkatesh Govindarajan, Paul K. Brindle, Ruth Ashery-Padan, David C. Beebe, Paul A. Overbeek, Ales Cvekl

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Lens induction is a classical embryologic model to study cell fate determination. It has been proposed earlier that specific changes in core histone modifications accompany the process of cell fate specification and determination. The lysine acetyltransferases CBP and p300 function as principal enzymes that modify core histones to facilitate specific gene expression. Herein, we performed conditional inactivation of both CBP and p300 in the ectodermal cells that give rise to the lens placode. Inactivation of both CBP and p300 resulted in the dramatic discontinuation of all aspects of lens specification and organogenesis, resulting in aphakia. The CBP/p300/ ectodermal cells are viable and not prone to apoptosis. These cells showed reduced expression of Six3 and Sox2, while expression of Pax6 was not upregulated, indicating discontinuation of lens induction. Consequently, expression of aB-and aA-crystallins was not initiated. Mutant ectoderm exhibited markedly reduced levels of histone H3 K18 and K27 acetylation, subtly increased H3 K27me3 and unaltered overall levels of H3 K9ac and H3 K4me3. Our data demonstrate that CBP and p300 are required to establish lens cell-type identity during lens induction, and suggest that posttranslational histone modifications are integral to normal cell fate determination in the mammalian lens.

Original languageEnglish
Pages (from-to)10199-10214
Number of pages16
JournalNucleic Acids Research
Volume41
Issue number22
DOIs
StatePublished - Dec 2013

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Histone Code
Post Translational Protein Processing
Lenses
Histones
Aphakia
Ectoderm
Crystallins
Organogenesis
Acetylation
Lysine Acetyltransferases
Apoptosis
Gene Expression

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Histone posttranslational modifications and cell fate determination : Lens induction requires the lysine acetyltransferases CBP and p300. / Wolf, Louise; Harrison, Wilbur; Huang, Jie; Xie, Qing; Xiao, Ningna; Sun, Jian; Kong, Lingkun; Lachke, Salil A.; Kuracha, Murali R.; Govindarajan, Venkatesh; Brindle, Paul K.; Ashery-Padan, Ruth; Beebe, David C.; Overbeek, Paul A.; Cvekl, Ales.

In: Nucleic Acids Research, Vol. 41, No. 22, 12.2013, p. 10199-10214.

Research output: Contribution to journalArticle

Wolf, L, Harrison, W, Huang, J, Xie, Q, Xiao, N, Sun, J, Kong, L, Lachke, SA, Kuracha, MR, Govindarajan, V, Brindle, PK, Ashery-Padan, R, Beebe, DC, Overbeek, PA & Cvekl, A 2013, 'Histone posttranslational modifications and cell fate determination: Lens induction requires the lysine acetyltransferases CBP and p300', Nucleic Acids Research, vol. 41, no. 22, pp. 10199-10214. https://doi.org/10.1093/nar/gkt824
Wolf, Louise ; Harrison, Wilbur ; Huang, Jie ; Xie, Qing ; Xiao, Ningna ; Sun, Jian ; Kong, Lingkun ; Lachke, Salil A. ; Kuracha, Murali R. ; Govindarajan, Venkatesh ; Brindle, Paul K. ; Ashery-Padan, Ruth ; Beebe, David C. ; Overbeek, Paul A. ; Cvekl, Ales. / Histone posttranslational modifications and cell fate determination : Lens induction requires the lysine acetyltransferases CBP and p300. In: Nucleic Acids Research. 2013 ; Vol. 41, No. 22. pp. 10199-10214.
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