Sci. Signal., 16 August 2011
Biochemistry Add Lipidation to Histone Modifications
Heather M. Thompson
Science Signaling, AAAS, Washington, DC 20005, USA
Histones, the protein component of nucleosomes around which DNA is wrapped as part of its packaging into chromatin, undergo various posttranslational modifications that affect their roles in DNA replication and repair and silencing or activation of gene regulation. Examples of histone posttranslational modifications include methylation, acetylation, and phosphorylation. Zou et al. found that histone H4 also undergoes O-palmitoylation. Immunofluorescent staining of cultured murine lung epithelial (MLE) cells revealed that acyl-CoA:lysophosphatidylcholine acyltransferase I (Lpcat1) translocated from the cytosol to the nucleus in response to Ca2+, where it colocalized with histone H4. Coimmunoprecipitation experiments from the nuclear fraction of MLE cell lysates revealed a nuclear Lpcat1–histone H4 complex. In vitro palmitoylation experiments demonstrated that histone H4 palmitoylation was catalyzed by Lpcat1 but not by a related palmitoyltransferase, serine palmitoyltransferase long chain base subunit 2 (SPTLC2), and that the site of palmitoylation in histone H4 was Ser47. Immunoprecipitation of histone H4 from lysates of MLE cells pulsed with radiolabeled palmitic acid or oleic acid revealed that Ca2+ stimulated histone H4 acylation with palmitic acid but not oleic acid. mRNA synthesis was globally decreased in cells expressing either a short hairpin RNA (shRNA) directed against Lpcat1 or a histone H4 Ser47Ala (S47A) mutant compared with cells transfected with a control shRNA plasmid or wild-type histone H4 plasmid, respectively. Together, these results suggest that Lpcat1-catalyzed O-palmitoylation of histone H4 is linked to Ca2+-stimulated increases in genome-wide transcription.
C. Zou, B. M. Ellis, R. M. Smith, B. B. Chen, Y. Zhao, R. K. Mallampalli, Acyl-CoA:lysophosphatidylcholine acyltransferase I (Lpcat1) catalyzes histone protein O-palmitoylation to regulate mRNA synthesis. J. Biol. Chem. 286, 28019–28025 (2011). [Abstract] [Full Text]
Citation: H. M. Thompson, Add Lipidation to Histone Modifications. Sci. Signal. 4, ec226 (2011).
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