Chromatin changes induced by lamin A/C deficiency and the histone deacetylase inhibitor trichostatin A

Galiová, Gabriela; Bártová, Eva; Raška, Ivan; Krejčí, Jana; Kozubek, Stanislav

doi:10.1016/j.ejcb.2008.01.013

Cited by 77 publications

(73 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The fact that these invaginations contain nuclear pore complexes and have been reported to contain translational machinery (Paytubi et al, 2009) further supports the notion of increased mRNA export and generation of proteins from active genes deep within the nucleus. Treatment with a histone deacetylase inhibitor actually increases the frequency of invaginations, which might be due to the increased abundance of transcriptionally active genes (Galiova et al, 2008). NR invaginations are also frequently reported as terminating at nucleoli (Fricker et al, 1997b;Schneider et al, 2010), which again might serve as tight spatial coupling between a transcriptionally active compartment and a potential transport channel.…”

Section: Discussionmentioning

confidence: 99%

The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

Goulbourne

Malhas

Vaux

2011

Journal of Cell Science

View full text Add to dashboard Cite

SummaryFarnesylated prelamin A accumulates when the final endoproteolytic maturation of the protein fails to occur and causes a dysmorphic nuclear phenotype; however, the morphology and mechanisms of biogenesis of these changes remain unclear. We show here that acute prelamin A accumulation after reduction in the activity of the ZMPSTE24 endoprotease by short interfering RNA knockdown, results in the generation of a complex nucleoplasmic reticulum that depends for its formation on the enzyme CTP:phosphocholinecytidylyltransferase-a (CCT-a, also known as choline-phosphate cytidylyltransferase A). This structure can form during interphase, confirming that it is independent of mitosis and therefore not a consequence of disordered nuclear envelope assembly. Serial-section dual-axis electron tomography reveals that these invaginations can take two forms: one in which the inner nuclear membrane infolds alone with an inter membrane space interior, and the other in which an invagination of both nuclear membranes occurs, enclosing a cytoplasmic core. Both types of invagination can co-exist in one nucleus and both are frequently studded with nuclear pore complexes (NPC), which reduces NPC abundance on the nuclear surface.

show abstract

Section: Discussionmentioning

confidence: 99%

The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

Goulbourne

Malhas

Vaux

2011

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…In contrast, H4K20 trimethylation is increased in laminopathy cells (Shumaker et al 2006). Loss of heterochromatin caused by lamin A/C deficiency is also associated with rearrangement and dispersion of HP1b and H3K9 methylation within the nucleoplasm (Filesi et al 2005;Galiová et al 2008). Similarly, inhibition of histone deacetylases, leading to decondensation of heterochromatin domains, is associated with nuclear reorganization of HP1 foci (Taddei et al 2001;Bártová et al 2005).…”

mentioning

confidence: 99%

Histone Modifications and Nuclear Architecture: A Review

Bártová

Krejčí

Harničárová

et al. 2008

J Histochem Cytochem.

Self Cite

312

193

View full text Add to dashboard Cite

S U M M A R Y Epigenetic modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and ADP ribosylation, of the highly conserved core histones, H2A, H2B, H3, and H4, influence the genetic potential of DNA. The enormous regulatory potential of histone modification is illustrated in the vast array of epigenetic markers found throughout the genome. More than the other types of histone modification, acetylation and methylation of specific lysine residues on N-terminal histone tails are fundamental for the formation of chromatin domains, such as euchromatin, and facultative and constitutive heterochromatin. In addition, the modification of histones can cause a region of chromatin to undergo nuclear compartmentalization and, as such, specific epigenetic markers are nonrandomly distributed within interphase nuclei. In this review, we summarize the principles behind epigenetic compartmentalization and the functional consequences of chromatin arrangement within interphase nuclei. (J Histochem Cytochem 56:711-721, 2008)

show abstract

“…Transforming chromatin to euchromatin will eventually require deacetylation by HDAC to return it to its heterochromatin state. With respect to HAT, lamin deficiency has been shown to cause increased HAT activity (23,34). When HAT activity results for both cell types were normalized to that of untreated control shRNA cells, we did indeed see acetylase activity in untreated lamin shRNA cells to be similar to those of sheared cells with intact lamina.…”

Section: Discussionmentioning

confidence: 74%

“…Trichostatin A, a class 1 HDAC inhibitor, has recently been shown to induce chromatin changes and relocate it away from the nuclear periphery, similar to what is observed in lamin A/C-deficient cells (34). TSA treatment of human umbilical vein endothelial cells resulted in suppressed eNOS expression (31).…”

Section: Discussionmentioning

confidence: 84%

“…Thus either inhibiting HDAC or silencing lamin A/C resulted in elevated, dexamethasone-induced transcriptional activity in BAEC. Disrupted lamina in lamin shRNA cells could affect transcription of GRE consensus genes via loss of HDAC functions and/or subsequent increased acetylation of HAT proteins (e.g., histone H3), as was observed for wild-type and lamin-deficient MEFs (34). Along with upregulation of anti-inflammatory genes, glucocorticoids also downregulate expression of inflammation associated genes such as interleuken-11, MAP3K14 (which stimulates NF-B activity), and CCL2 (participates in the pathogenesis of atherosclerosis) (60).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation

Nayebosadri

2013

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Nayebosadri A, Ji JY. Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation. Am J Physiol Cell Physiol 305: C309 -C322, 2013. First published May 22, 2013; doi:10.1152/ajpcell.00293.2012The lamina serves to maintain the nuclear structure and stiffness while acting as a scaffold for heterochromatin and many transcriptional proteins. Its role in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In this study, we successfully silenced lamin A/C in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to dexamethasone and shear stress. Nuclear translocation of GR, an antiinflammatory nuclear receptor, in response to dexamethasone or shear stress (5, 10, and 25 dyn/cm 2 ) was observed via time-lapse cell imaging and quantified using a Bayesian image analysis algorithm. Transcriptional activity of the GRE promoter was assessed using a dual-luciferase reporter plasmid. We found no dependence on nuclear lamina for GR translocation from the cytoplasm into the nucleus. However, the absence of lamin A/C led to significantly increased expression of luciferase under dexamethasone and shear stress induction as well as changes in histone protein function. PCR results for NF-B inhibitor alpha (NF-BIA) and dual specificity phosphatase 1 (DUSP1) genes further supported our luciferase data with increased expression in the absence of lamin. Our results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus, but nuclear lamina is important to properly regulate GRE transcription. Nuclear lamina, rather than histone deacetylase (HDAC), is a more significant mediator of shear stress-induced transcriptional activity, while dexamethasone-initiated transcription is more HDAC dependent. Our findings provide more insights into the molecular pathways involved in nuclear mechanotransduction. glucocorticoid receptor; nuclear lamina; shear stress; dexamethasone; endothelial cells CARDIOVASCULAR DISEASES SUCH as atherosclerosis are the leading cause of death in the United States. The initiation and development of atherosclerosis are typically associated with endothelial dysfunction (20,51). Endothelial cells at the lumen of blood vessels are continuously exposed to both hemodynamic shear stress and cyclic stretch due to blood flow (16). The distinct local hemodynamic profiles influence endothelial behaviors in the vasculature. Atherosclerotic lesions tend to develop at regions of disturbed flow and low shear stress at bifurcation sites and curvatures, while regions with uniform high laminar shear stress are protected (10,48,66). Endothelial responses to shear stress can be categorized as immediate [rapid release of nitric oxide (NO); (49)] as well as short-term

show abstract

Chromatin changes induced by lamin A/C deficiency and the histone deacetylase inhibitor trichostatin A

Cited by 77 publications

References 64 publications

The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

Histone Modifications and Nuclear Architecture: A Review

Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation

Contact Info

Product

Resources

About