The Dimeric Structure and the Bivalent Recognition of H3K4me3 by the Tumor Suppressor ING4 Suggests a Mechanism for Enhanced Targeting of the HBO1 Complex to Chromatin

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• 作者：Alicia Palacios ; Alberto Moreno ; Bruno L. Oliveira ; Teresa Rivera ; Jesú ; s Prieto ; Pascal Garcí ; a ; M. Rosario Ferná ; ndez-Ferná ; ndez ; Pau Bernadó ; Ignacio Palmero ; Francisco J. Blan
• 关键词：ING4 structure ; histone tail ; chromatin ; NMR ; SAXS
• 刊名：Journal of Molecular Biology
• 出版年：2010
• 出版时间：5 March 2010
• 年：2010
• 卷：396
• 期：4
• 页码：1117-1127
• 全文大小：1084 K

文摘

The INhibitor of Growth (ING) family of tumor suppressors regulates the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at position K4 (H3K4me3). This modification is recognized by the plant homeodomain (PHD) present at the C-terminus in the five members of the ING family. ING4 facilitates histone H3 acetylation by the HBO1 complex. Here, we show that ING4 forms homodimers through its N-terminal domain, which folds independently into an elongated coiled-coil structure. The central region of ING4, which contains the nuclear localization sequence, is disordered and flexible and does not directly interact with p53, or does it with very low affinity, in contrast to previous findings. The NMR analysis of the full-length protein reveals that the two PHD fingers of the dimer are chemically equivalent and independent of the rest of the molecule. The detailed NMR analysis of the full-length dimeric protein binding to histone H3K4me3 shows essentially the same binding site and affinity as the isolated PHD finger. Therefore, the ING4 dimer has two identical and independent binding sites for H3K4me3 tails, which, in the context of the chromatin, could belong to the same or to different nucleosomes. These results show that ING4 is a bivalent reader of the chromatin H3K4me3 modification and suggest a mechanism for enhanced targeting of the HBO1 complex to specific chromatin sites. This mechanism could be common to other ING-containing remodeling complexes.