Modulation of HMG‐N2 binding to chromatin by butyrate‐induced acetylation in human colon adenocarcinoma cells

Lührs, Hardi; Hock, Robert; Schauber, Jürgen; Weihrauch, M.; Harrer, Monika; Melcher, Ralph; Scheppach, Wolfgang; Bustin, Michael; Menzel, Thomas

doi:10.1002/ijc.10098

Cited by 22 publications

(16 citation statements)

References 47 publications

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“…These data demonstrate for the first time that NaAsO 2 regulates the dynamics of chromatin-binding proteins in living cells. This finding is consistent with previous investigations that showed increased HMGN dynamics after TSA or butyrate treatment (Lührs et al 2002). Along with the induction of global histone hyperacetylation, these results validate the induction of an open chromatin state by NaAsO 2 .…”

Section: Naaso 2 Influences Particular Histone Modificationssupporting

confidence: 93%

“…After three washing steps in TBST (10 min each), nitrocellulose membranes were incubated with peroxidase conjugated secondary antibodies in 5% non-fat dry milk in TBST. Washing and detection was performed as described (Lührs et al 2002). Dilutions of antibodies were 1:10,000 for H3K9ac and H4K20me3, 1:5,000 for H3K4me2, H3K4me3, H3K9me2, H3K9me3, and 1:2,000 for H3K27me3, respectively.…”

Section: Immunoblot Analysismentioning

confidence: 99%

“…Equal numbers of nuclei (0.1× 10 6 ) were loaded per lane. Sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) and transfer onto nitrocellulose was performed as described previously (Lührs et al 2002). To compare loading and efficiency of transfer, the nitrocellulose was stained with Ponceau S. Blocking was carried out with 5% non-fat dry milk in Tris-buffered saline Tween-20 (TBST) for 1 h before the first antibodies incubation, except for H3K27me3, which was blocked with 3% bovine serum albumin (BSA)/TBST.…”

Section: Immunoblot Analysismentioning

confidence: 99%

“…Cell nuclei from HepG2 were isolated and counted as described (Lührs et al 2002). Equal numbers of nuclei (0.1× 10 6 ) were loaded per lane.…”

Section: Immunoblot Analysismentioning

confidence: 99%

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Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells

et al. 2007

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Extensive epidemiological data indicate that inorganic arsenic is associated with several types of human cancer. Nevertheless, the underlying mechanisms are poorly understood. Among its mode of action are the alterations on DNA methylation, which provoke aberrant gene expression. However, beyond DNA methylation, little is known about arsenic's effects on chromatin. In this study, we investigated the effects of sodium arsenite (NaAsO(2)) on global histone modifications and nucleosome-associated proteins. Our findings revealed that NaAsO(2) exposure significantly increases global histone acetylation. This effect was related to the inhibition of histone deacetylase (HDAC) activity because NaAsO(2) was able to inhibit HDACs comparable to the well-known HDAC inhibitor trichostatin A (TSA). Furthermore, analyses of the dynamic properties of the nucleosome-associated high mobility group N proteins demonstrate that NaAsO(2) elevates their mobility. Thus, our data suggest that NaAsO(2) induces chromatin opening by histone hyperacetylation due to HDAC inhibition and increase of the mobility of nucleosome-associated proteins. As the chromatin compaction is crucial for the regulation of gene expression as well as for genome stability, we propose that chromatin opening by NaAsO(2) may play a significant role to impart its genotoxic effects.

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Section: Naaso 2 Influences Particular Histone Modificationssupporting

confidence: 93%

Section: Immunoblot Analysismentioning

confidence: 99%

Section: Immunoblot Analysismentioning

confidence: 99%

“…Cell nuclei from HepG2 were isolated and counted as described (Lührs et al 2002). Equal numbers of nuclei (0.1× 10 6 ) were loaded per lane.…”

Section: Immunoblot Analysismentioning

confidence: 99%

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Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells

et al. 2007

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“…The consequence of non-histone protein acetylation is subtle and variable. It can result in either increasing (14 -16) or decreasing (17)(18)(19)(20) DNA binding affinity and transcriptional activation (21). Such diverse effects on transcription activities could be dependent on the acetylation sites in different functional domains of nuclear receptors that affect DNA binding affinity, protein stability, and receptor-coregulator interaction (19,(21)(22)(23)(24).…”

Section: The Androgen Receptor (Ar)mentioning

confidence: 99%

Increased Acetylation in the DNA-binding Domain of TR4 Nuclear Receptor by the Coregulator ARA55 Leads to Suppression of TR4 Transactivation

Xie

Lee

et al. 2011

Journal of Biological Chemistry

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The nuclear receptor TR4 is a key regulator for many physiological processes, including growth, development, and metabolism. However, how the transcriptional activity of TR4 is regulated in the absence of ligand(s) remains largely unknown. Here we found that an androgen receptor (AR) coactivator, ARA55, might function as a corepressor to suppress TR4 transactivation. Molecular mechanistic dissection with mutation analysis found that ARA55 could enhance TR4 acetylation at the conserved acetylation sites of lysine 175 and lysine 176 in the DNAbinding domain via recruiting proteins with histone acetyl transferase activity, which might then reduce significantly the TR4 DNA binding activity that resulted in the suppression of TR4 transactivation. These results are in contrast to the classic ARA55 coactivator function to enhance AR transactivation partially via increased AR acetylation in the hinge/ligand-binding domain. Together, these results not only provide a novel functional mechanism showing that acetylation of different nuclear receptors at different domains by coregulator may lead to differential receptor transactivation activity but also provide a new way for small molecules to control TR4 transactivation via altering TR4 acetylation levels, and such small molecules may have potential therapeutic applications in the future. The androgen receptor (AR)2 -associated protein ARA55 is a nuclear receptor coactivator (1, 2) that belongs to the group III LIM domain-containing protein family (3), which can function as molecular adaptors to stabilize protein complexes (4, 5). First identified as an AR coactivator (1, 2), ARA55 could also enhance the transactivation of other nuclear receptors, such as glucocorticoid receptor (6) and peroxisome proliferator-activated receptor ␥ (7). ARA55 lacks histone acetyltransferase (HAT) or methyltransferase activity (5). However, ARA55, with four LIM domains within its amino terminus, could still be able to influence acetylation on nuclear receptors via recruitment of histone acetyltransferase-containing coactivators, such as CBP and p300 (5). ARA55 also recruits corepressor complexes to glucocorticoid-responsive promoters in the absence of ligands (7), suggesting that ARA55 may be able to coordinate corepressor release, as well as coactivator recruitment upon glucocorticoid ligand stimulation.An important mechanism by which ARA55 enhances AR transactivation is that ARA55 serves as a bridge protein to recruit HATs, such as CBP/p300 (8). Acetylation of the histones by HATs promotes chromatin structural changes that result in the promotion of gene transactivation (9). CBP/p300 can also acetylate AR on conserved lysines located in the hinge/ligandbinding domain (LBD). A recent genomic study identified 3600 lysine acetylation sites on 1750 proteins (10), suggesting that protein acetylation could be as common as protein phosphorylation to alter or influence protein function (11). Indeed, almost all of the enzymes involved in human or yeast metabolic processes are acetylated (12, 13). Th...

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Trend of Histone Deacetylase Inhibitors in Cancer Therapy: Isoform Selectivity or Multitargeted Strategy

Zhang

Han

Jiang

et al. 2014

Medicinal Research Reviews

118

104

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Pharmacological inhibition of histone deacetylases (HDACs) has been successfully applied in the treatment of a wide range of disorders, including Parkinson's disease, infection, cardiac diseases, inflammation, and especially cancer. HDAC inhibitors (HDACIs) have been proved to be effective antitumor agents by various stages of investigation. At present, there are two opposite focuses of HDACI design in the cancer therapy, highly selective inhibitor strategy and dual- or multitargeted inhibitors. The former method, which is supposed to elucidate the function of individual HDAC and provide candidate inhibitors with fewer side effects, has been widely accepted by the inhibitor developer. The latter approach, though less practiced, has promising potential for the antitumor therapy based on HDACIs. Effective HDACIs, some of which are in clinic anticancer research, have been developed by both methods. In order to gain insight into HDACI design, the strategies and achievements of the two diverse methods are reviewed.

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Modulation of HMG‐N2 binding to chromatin by butyrate‐induced acetylation in human colon adenocarcinoma cells

Cited by 22 publications

References 47 publications

Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells

Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells

Increased Acetylation in the DNA-binding Domain of TR4 Nuclear Receptor by the Coregulator ARA55 Leads to Suppression of TR4 Transactivation

Trend of Histone Deacetylase Inhibitors in Cancer Therapy: Isoform Selectivity or Multitargeted Strategy

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