Lim, J. H. et al. Chromosomal protein HMGN1 enhances the acetylation of lysine 14 in histone H3. EMBO J. 24, 3038-3048

Protein Section, Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
The EMBO Journal (Impact Factor: 10.43). 10/2005; 24(17):3038-48. DOI: 10.1038/sj.emboj.7600768
Source: PubMed


The acetylation levels of lysine residues in nucleosomes, which are determined by the opposing activities of histone acetyltransferases (HATs) and deacetylases, play an important role in regulating chromatin-related processes, including transcription. We report that HMGN1, a nucleosomal binding protein that reduces the compaction of the chromatin fiber, increases the levels of acetylation of K14 in H3. The levels of H3K14ac in Hmgn1-/- cells are lower than in Hmgn1+/+ cells. Induced expression of wild-type HMGN1, but not of a mutant that does not bind to chromatin, in Hmgn1-/- cells elevates the levels of H3K14ac. In vivo, HMGN1 elevates the levels of H3K14ac by enhancing the action of HAT. In vitro, HMGN1 enhances the ability of PCAF to acetylate nucleosomal, but not free, H3. Thus, HMGN1 modulates the levels of H3K14ac by binding to chromatin. We suggest that HMGN1, and perhaps similar architectural proteins, modulates the levels of acetylation in chromatin by altering the equilibrium generated by the opposing enzymatic activities that continuously modify and de-modify the histone tails in nucleosomes.

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Available from: Michael Bergel, May 14, 2014
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    • "These involve the essential function of the Swi2/Snf2-like CSB protein, which has also been shown to have chromatin remodeling activity (Citterio et al. 2000), the CSB-dependent recruitment of chromatin regulators such as the histone acetyltransferase (HAT) p300 (Fousteri et al. 2006), and the enhancement of TC-NER on treatment of cells with histone deacetylase inhibitors (Smerdon et al. 1982). Equally important is the recruitment of the nucleosomal nonhistone binding protein HMGN1 in a CSB-and CSA-dependent manner (Fousteri et al. 2006), which is known to increase HAT activity and unwind chromatin (Trieschmann et al. 1998; Lim et al. 2005). Notably, HMGN1 2/2 MEFs display enhanced UV sensitivity and show delayed removal of CPDs from the transcribed strand of active genes (Birger et al. 2003). "
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    ABSTRACT: Transcriptional arrest caused by DNA damage is detrimental for cells and organisms as it impinges on gene expression and thereby on cell growth and survival. To alleviate transcriptional arrest, cells trigger a transcription-dependent genome surveillance pathway, termed transcription-coupled nucleotide excision repair (TC-NER) that ensures rapid removal of such transcription-impeding DNA lesions and prevents persistent stalling of transcription. Defective TC-NER is causatively linked to Cockayne syndrome, a rare severe genetic disorder with multisystem abnormalities that results in patients' death in early adulthood. Here we review recent data on how damage-arrested transcription is actively coupled to TC-NER in mammals and discuss new emerging models concerning the role of TC-NER-specific factors in this process.
    Cold Spring Harbor perspectives in biology 08/2013; 5(8). DOI:10.1101/cshperspect.a012625 · 8.68 Impact Factor
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    • "that does not bind to chromatin, in these cells restored normal acetylation [37]. HMGN1 enhances the levels of H3K14Ac by stimulating HAT activity rather than by inhibiting HDAC activity [37]. Subsequent studies indicated that HMGN1-stimulated enhancement of H3K14Ac levels optimizes the cellular response to heat shock, as determined by the levels of Hsp70 transcripts [38]. "
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    ABSTRACT: The HMGN family of proteins binds to nucleosomes without any specificity for the underlying DNA sequence. They affect the global and local structure of chromatin, as well as the levels of histone modifications and thus play a role in epigenetic regulation of gene expression. This review focuses on the recent studies that provide new insights on the interactions between HMGN proteins, nucleosomes, and chromatin, and the effects of these interactions on epigenetic and transcriptional regulation. This article is part of a Special Issue entitled: Chromatin in time and space.
    Biochimica et Biophysica Acta 02/2012; 1819(7):652-6. DOI:10.1016/j.bbagrm.2012.01.013 · 4.66 Impact Factor
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    • "The 2.7 kb acetylated histone peak that spans the promoter and first untranslated exon, and part of intron 1 of KIAA0319 was identified by chromatin immunoprecipitation (ChIP) combined with detection by microarrays (ChIP-chip) using an antibody recognizing H3Ac at K9/K14 in a human retinoblastoma cell-line Y79. H3K9ac and H3K14ac are well-studied markers of accessible chromatin, which often contain regulatory elements (Liang et al. 2004; Bernstein et al. 2005; Lim et al. 2005; Kratz et al. 2010). This acetylated histone peak in KIAA0319 was also observed in six mouse tissues (Couto et al. 2010), and as a 2.3 kb peak in two additional human cell lines, a neuroblastoma SH-SY5Y and a glioblastoma, A-172 by ChIP-sequencing (unpublished). "
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