scholarly journals Chromosome Y pericentric heterochromatin is a primary target of HSF1 in male cells

Chromosoma ◽  
2021 ◽  
Vol 130 (1) ◽  
pp. 53-60
Author(s):  
Jessica Penin ◽  
Solenne Dufour ◽  
Virginie Faure ◽  
Sabrina Fritah ◽  
Daphné Seigneurin-Berny ◽  
...  
Keyword(s):  
Heat Shock ◽  
Transcriptional Activation ◽  
Human Fibroblasts ◽  
Pericentric Heterochromatin ◽  
Chromosome 9 ◽  
Nuclear Accumulation ◽  
Critical Element ◽  
Heat Shock Factor 1 ◽  
Primary Target ◽  
Chromosome Y

AbstractThe heat shock factor 1 (HSF1)-dependent transcriptional activation of human pericentric heterochromatin in heat-shocked cells is the most striking example of transcriptional activation of heterochromatin. Until now, pericentric heterochromatin of chromosome 9 has been identified as the primary target of HSF1, in both normal and tumor heat-shocked cells. Transcriptional awakening of this large genomic region results in the nuclear accumulation of satellite III (SATIII) noncoding RNAs (ncRNAs) and the formation in cis of specific structures known as nuclear stress bodies (nSBs). Here, we show that, in four different male cell lines, including primary human fibroblasts and amniocytes, pericentric heterochromatin of chromosome Y can also serve as a unique primary site of HSF1-dependent heterochromatin transcriptional activation, production of SATIII ncRNA, and nucleation of nuclear stress bodies (nSBs) upon heat shock. Our observation suggests that the chromosomal origin of SATIII transcripts in cells submitted to heat shock is not a determinant factor as such, but that transcription of SATIII repetitive units or the SATIII ncRNA molecules is the critical element of HSF1-dependent transcription activation of constitutive heterochromatin.

scholarly journals Transcriptional Activation of a Constitutive Heterochromatic Domain of the Human Genome in Response to Heat Shock

2004 ◽  
Vol 15 (2) ◽  
pp. 543-551 ◽  
Author(s):  
Nicoletta Rizzi ◽  
Marco Denegri ◽  
Ilaria Chiodi ◽  
Margherita Corioni ◽  
Rut Valgardsdottir ◽  
...  
Keyword(s):  
Heat Shock ◽  
Transcriptional Activation ◽  
Chromosome 9 ◽  
Heat Shock Factor 1 ◽  
Histone H4 ◽  
Rna Molecules ◽  
Histone H4 Acetylation ◽  
Response To Stress ◽  
Acetylated Histone H4 ◽  
Processing Factors

Heat shock triggers the assembly of nuclear stress bodies that contain heat shock factor 1 and a subset of RNA processing factors. These structures are formed on the pericentromeric heterochromatic regions of specific human chromosomes, among which chromosome 9. In this article we show that these heterochromatic domains are characterized by an epigenetic status typical of euchromatic regions. Similarly to transcriptionally competent portions of the genome, stress bodies are, in fact, enriched in acetylated histone H4. Acetylation peaks at 6 h of recovery from heat shock. Moreover, heterochromatin markers, such as HP1 and histone H3 methylated on lysine 9, are excluded from these nuclear districts. In addition, heat shock triggers the transient accumulation of RNA molecules, heterogeneous in size, containing the subclass of satellite III sequences found in the pericentromeric heterochromatin of chromosome 9. This is the first report of a transcriptional activation of a constitutive heterochromatic portion of the genome in response to stress stimuli.

Inhibition of Heat Shock Factor 1 Enhances Repressive Molecular Mechanisms on the POMC Promoter

2019 ◽  
Vol 109 (4) ◽  
pp. 362-373
Author(s):  
Denis Ciato ◽  
Ran Li ◽  
Jose Luis Monteserin Garcia ◽  
Lilia Papst ◽  
Sarah D’Annunzio ◽  
...  
Keyword(s):  
Heat Shock ◽  
Clinical Features ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Primary Cultures ◽  
Heat Shock Protein 90 ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Promising Treatment ◽  
Acth Secreting

Background: Cushing’s disease (CD) is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. They express high levels of heat shock protein 90 and heat shock factor 1 (HSF1) in comparison to the normal tissue counterpart, indicating activated cellular stress. Aims: Our objectives were: (1) to correlate HSF1 expression with clinical features and hormonal/radiological findings of CD, and (2) to investigate the effects of HSF1 inhibition as a target for CD treatment. Patients/Methods: We examined the expression of total and pSer326HSF1 (marker for its transcriptional activation) by Western blot on eight human CD tumours and compared to the HSF1 status of normal pituitary. We screened a cohort of 45 patients with CD for HSF1 by immunohistochemistry and correlated the HSF1 immunoreactivity score with the available clinical data. We evaluated the effects of HSF1 silencing with RNA interference and the HSF1 inhibitor KRIBB11 in AtT-20 cells and four primary cultures of human corticotroph tumours. Results: We show that HSF1 protein is highly expressed and transcriptionally active in CD tumours in comparison to normal pituitary. The immunoreactivity score for HSF1 did not correlate with the typical clinical features of the disease. HSF1 inhibition reduced proopiomelanocortin (Pomc) transcription in AtT-20 cells. The HSF1 inhibitor KRIBB11 suppressed ACTH synthesis from 75% of human CD tumours in primary cell culture. This inhibitory action on Pomc transcription was mediated by increased glucocorticoid receptor and suppressed Nurr77/Nurr1 and AP-1 transcriptional activities. Conclusions: These data show that HSF1 regulates POMC transcription. Pharmacological targeting of HSF1 may be a promising treatment option for the control of excess ACTH secretion in CD.

scholarly journals Human Chromosomes 9, 12, and 15 Contain the Nucleation Sites of Stress-Induced Nuclear Bodies

2002 ◽  
Vol 13 (6) ◽  
pp. 2069-2079 ◽  
Author(s):  
Marco Denegri ◽  
Daniela Moralli ◽  
Mariano Rocchi ◽  
Marco Biggiogera ◽  
Elena Raimondi ◽  
...  
Keyword(s):  
Heat Shock ◽  
Human Cell ◽  
Hela Cells ◽  
Heat Shock Factor ◽  
Nuclear Bodies ◽  
Chromosome 9 ◽  
Heat Shock Factor 1 ◽  
Human Chromosomes ◽  
Cell Hybrids ◽  
Nucleation Sites

We previously reported the identification of a novel nuclear compartment detectable in heat-shocked HeLa cells that we termed stress-induced Src-activated during mitosis nuclear body (SNB). This structure is the recruitment center for heat shock factor 1 and for a number of RNA processing factors, among a subset of Serine-Arginine splicing factors. In this article, we show that stress-induced SNBs are detectable in human but not in hamster cells. By means of hamster>human cell hybrids, we have identified three human chromosomes (9, 12, and 15) that are individually able to direct the formation of stress bodies in hamster cells. Similarly to stress-induced SNB, these bodies are sites of accumulation of hnRNP A1-interacting protein and heat shock factor 1, are usually associated to nucleoli, and consist of clusters of perichromatin granules. We show that the p13-q13 region of human chromosome 9 is sufficient to direct the formation of stress bodies in hamster>human cell hybrids. Fluorescence in situ hybridization experiments demonstrate that the pericentromeric heterochromatic q12 band of chromosome 9 and the centromeric regions of chromosomes 12 and 15 colocalize with stress-induced SNBs in human cells. Our data indicate that human chromosomes 9, 12, and 15 contain the nucleation sites of stress bodies in heat-shocked HeLa cells.

scholarly journals Intramolecular Repression of Mouse Heat Shock Factor 1

1998 ◽  
Vol 18 (2) ◽  
pp. 906-918 ◽  
Author(s):  
Thomas Farkas ◽  
Yulia A. Kutskova ◽  
Vincenzo Zimarino
Keyword(s):  
Heat Shock ◽  
Transcriptional Activation ◽  
Mammalian Cells ◽  
Coiled Coil ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Reticulocyte Lysate ◽  
Heptad Repeats ◽  
Intramolecular Mechanism

ABSTRACT The pathway leading to transcriptional activation of heat shock genes involves a step of heat shock factor 1 (HSF1) trimerization required for high-affinity binding of this activator protein to heat shock elements (HSEs) in the promoters. Previous studies have shown that in vivo the trimerization is negatively regulated at physiological temperatures by a mechanism that requires multiple hydrophobic heptad repeats (HRs) which may form a coiled coil in the monomer. To investigate the minimal requirements for negative regulation, in this work we have examined mouse HSF1 translated in rabbit reticulocyte lysate or extracted from Escherichia coli after limited expression. We show that under these conditions HSF1 behaves as a monomer which can be induced by increases in temperature to form active HSE-binding trimers and that mutations of either HR region cause activation in both systems. Furthermore, temperature elevations and acidic buffers activate purified HSF1, and mild proteolysis excises fragments which form HSE-binding oligomers. These results suggest that oligomerization can be repressed in the monomer, as previously proposed, and that repression can be relieved in the apparent absence of regulatory proteins. An intramolecular mechanism may be central for the regulation of this transcription factor in mammalian cells, although not necessarily sufficient.

scholarly journals Heat Shock Factor 1 Represses Ras-induced Transcriptional Activation of the c-fosGene

1997 ◽  
Vol 272 (43) ◽  
pp. 26803-26806 ◽  
Author(s):  
Changmin Chen ◽  
Yue Xie ◽  
Mary Ann Stevenson ◽  
Philip E. Auron ◽  
Stuart K. Calderwood
Keyword(s):  
Heat Shock ◽  
Transcriptional Activation ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1

scholarly journals Heat shock of human synovial and dermal fibroblasts induces delayed up-regulation of collagenase-gene expression

1995 ◽  
Vol 308 (3) ◽  
pp. 743-747 ◽  
Author(s):  
E G Hitraya ◽  
J Varga ◽  
S A Jimenez
Keyword(s):  
Gene Expression ◽  
Heat Shock ◽  
Binding Site ◽  
Transcriptional Activation ◽  
Human Fibroblasts ◽  
Dermal Fibroblasts ◽  
Mrna Levels ◽  
Hsp 70 ◽  
Mobility Shift ◽  
Collagenase Gene

We investigated the effect of heat shock on the expression of the collagenase gene in normal human synovial and dermal fibroblasts. Heat shock (42-44 degrees C for 1 h) caused a marked increase in heat-shock protein 70 (HSP-70) mRNA levels, followed by a delayed increase in collagenase mRNA levels, in both cell types. Pretreatment with cycloheximide had no effect on the heat-shock-induced increase in HSP-70 mRNA expression, but abrogated the induction of collagenase mRNA during the recovery. To study the mechanisms of collagenase-gene induction by heat shock, the transcriptional activity of a collagenase-promoter-driven chloramphenicol acetyltransferase (CAT) reporter gene was examined in transient transfection experiments. Heat shock was followed by a > 2-fold increase in CAT activity driven by a 3.8 kb fragment of the collagenase promoter, or by a construct containing an AP-1 binding site. A mutation in the AP-1 binding site abolished the effect of heat shock. Electrophoretic-mobility-shift assays revealed a marked increase in DNA-binding activity specific for the AP-1 binding site in nuclear extracts prepared from synovial fibroblasts recovering from heat shock. These results indicate that heat shock causes a delayed increase in collagenase-gene expression in human fibroblasts, and suggests that this stimulation involves, at least in part, transcriptional activation through an AP-1 binding site. Heat shock appears to initiate a programme of cellular events resulting in collagenase-gene expression, and therefore may contribute to connective-tissue degradation in disease states.

Radicicol activates heat shock protein expression and cardioprotection in neonatal rat cardiomyocytes

2004 ◽  
Vol 287 (3) ◽  
pp. H1081-H1088 ◽  
Author(s):  
Tina M. Griffin ◽  
Tina V. Valdez ◽  
Ruben Mestril
Keyword(s):  
Heat Shock ◽  
Transcriptional Activation ◽  
Cardiac Tissue ◽  
Defense Mechanism ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neonatal Rat ◽  
Heat Shock Factor 1 ◽  
Rat Cardiomyocytes ◽  
Neonatal Rat Cardiomyocytes

Heat shock proteins (HSPs) constitute an endogenous cellular defense mechanism against environmental stresses. In the past few years, studies have shown that overexpression of HSPs can protect cardiac myocytes against ischemia-reperfusion injury. In an attempt to increase the HSPs in cardiac tissue, we used the compound radicicol that activates HSP expression by binding to the HSP 90 kDa (HSP90). HSP90 is the main component of the cytosolic molecular chaperone complex, which has been implicated in the regulation of the heat shock factor 1 (HSF1). HSF1 is responsible for the transcriptional activation of the heat shock genes. In the present study, we show that radicicol induces HSP expression in neonatal rat cardiomyocytes, and this increase in HSPs confers cardioprotection to these cardiomyocytes. We also show that radicicol induction of the HSP and cardioprotection is dependent on the inhibition of HSP90 in cardiomyocytes. These results indicate that modulation of the active HSP90 protein level plays an important role in cardioprotection. Therefore, compounds, such as radicicol and its possible derivatives that inhibit the function of HSP90 in the cell may represent potentially useful cardioprotective agents.

Sign in / Sign up

Export Citation Format

Share Document