Details

Autor(en) / Beteiligte

• Thomas, Colin J.
• Kotova, Elena
• Andrake, Mark
• Adolf-Bryfogle, Jared
• Glaser, Robert
• Regnard, Catherine
• Tulin, Alexei V.

Titel

Kinase-Mediated Changes in Nucleosome Conformation Trigger Chromatin Decondensation via Poly(ADP-Ribosyl)ation

Ist Teil von

• Molecular cell, 2014-03, Vol.53 (5), p.831-842

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Dynamically controlled posttranslational modifications of nucleosomal histones alter chromatin condensation to regulate transcriptional activation. We report that a nuclear tandem kinase, JIL-1, controls gene expression by activating poly(ADP-ribose) polymerase-1 (PARP-1). JIL-1 phosphorylates the C terminus of the H2Av histone variant, which stimulates PARP-1 enzymatic activity in the surrounding chromatin, leading to further modification of histones and chromatin loosening. The H2Av nucleosome has a higher surface representation of PARP-1 binding patch, consisting of H3 and H4 epitopes. Phosphorylation of H2Av by JIL-1 restructures this surface patch, leading to activation of PARP-1. Exposure of Val61 and Leu23 of the H4 histone is critical for PARP-1 binding on nucleosome and PARP-1 activation following H2Av phosphorylation. We propose that chromatin loosening and associated initiation of gene expression is activated by phosphorylation of H2Av in a nucleosome positioned in promoter regions of PARP-1-dependent genes. [Display omitted] •JIL-1 kinase is required for PARP-1 activation in vivo•JIL-1 activates PARP-1 via H2AvSer137 phosphorylation at promoters•PARP-1 binds to the H2Av nucleosome via the hydrophobic patch formed by histone H4•Phosphorylation of H2AvSer137 activates PARP-1 by increasing the accessibility of H4 Thomas et al. show that poly(ADP-ribose) polymerase-1 (PARP-1) is the primary regulator of chromatin structure. Phosphorylation of a histone variant by a signaling kinase leads to structural changes in a nucleosome and PARP-1 activation, which in turn loosens chromatin around promoter regions to activate transcription.