CoREST Represses the Heat Shock Response Mediated by HSF1

Gómez, Andrea V.; Galleguillos, Danny; Maass, Juan C.; Battaglioli, Elena; Kukuljan, Manuel; Andrés, Marı́a Estela

doi:10.1016/j.molcel.2008.06.015

Cited by 40 publications

(27 citation statements)

References 52 publications

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“…2B, Lower). The specificity was confirmed by the negative interaction of CRF-BP with the C-terminal domain of the κ-opioid receptor (Cter-KOR), another GPCR and the positive interaction between corepressor for RE1 silencing transcription factor (CoREST) and heat shock protein 70 (Hsp70) (34). Transformed yeasts viability was shown by growing them in noninteraction selecting medium (Fig.…”

Section: Significancementioning

confidence: 93%

CRF binding protein facilitates the presence of CRF type 2α receptor on the cell surface

Slater

Cerda

Pereira

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Corticotropin releasing factor binding protein (CRF-BP) was originally recognized as CRF sequestering protein. However, its differential subcellular localization in different brain nuclei suggests that CRF-BP may have additional functions. There is evidence that CRF-BP potentiates CRF and urocortin 1 actions through CRF type 2 receptors (CRF 2 R). CRF 2 R is a G protein-coupled receptor (GPCR) that is found mainly intracellularly as most GPCRs. The access of GPCRs to the cell surface is tightly regulated by escort proteins. We hypothesized that CRF-BP binds to CRF 2 R, exerting an escort protein role. We analyzed the colocalization of CRF-BP and CRF 2 R in cultured rat mesencephalic neurons, and the localization and interaction of heterologous expressed CRF-BP and CRF 2α R in yeast, human embryonic kidney 293, and rat pheochromocytoma 12 cells. Our results showed that CRF-BP and CRF 2 R naturally colocalize in the neurites of cultured mesencephalic neurons. Heterologous expression of each protein showed that CRF-BP was localized mainly in secretory granules and CRF 2α R in the endoplasmic reticulum. In contrast, CRF-BP and CRF 2α R colocalized when both proteins are coexpressed. Here we show that CRF-BP physically interacts with the CRF 2α R but not the CRF 2β R isoform, increasing CRF 2α R on the cell surface. Thus, CRF-BP emerges as a GPCR escort protein increasing the understanding of GPCR trafficking.T he corticotropin releasing factor (CRF) system plays a key role in the response and adaptation to stressful stimuli (1, 2) and in the interaction between stress and addiction (3). The CRF system acts on the hypothalamic-pituitary-adrenal axis (4, 5) and in different brain regions (1, 6). The CRF system includes four peptides, CRF type 1 (CRF 1 R) and type 2 (CRF 2 R), G protein-coupled receptors (GPCRs) (6-8), and CRF binding protein (CRF-BP) (9). CRF-BP was described as a circulating polypeptide in pregnant women (10, 11). CRF-BP binds CRF and urocortin with high affinity (12). Different functions have been proposed for CRF-BP (13). On one hand, CRF-BP exerts an inhibitory role by sequestering CRF peptide (9, 14-16). On other hand, a facilitatory role of CRF-BP on CRF-dependent neuronal plasticity depending on CRF 2 R in the rat ventral tegmental area (VTA) has been described (17, 18). Recently, it has been shown that CRF-BP and CRF 2 R are important for ethanol binge drinking behavior (19). The anatomical evidence showing that CRF-BP has different subcellular distribution depending on the neuronal context (20) further supports several roles for CRF-BP.Three isoforms of CRF 2 R have been reported, the α isoform being the most expressed in the brain (21). CRF 2α R is localized intracellularly in neurons of the rat dorsal raphe nucleus and that exposure to acute (22) and repeated stress (23) increases its presence in the plasma membrane. CRF 2α R overexpressed in human embryonic kidney (HEK293T) cells is associated with the endoplasmic reticulum (ER) (24). Schulz et al. (25) showed that CRF 2α R is retained in...

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Section: Significancementioning

confidence: 93%

CRF binding protein facilitates the presence of CRF type 2α receptor on the cell surface

Slater

Cerda

Pereira

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…HEK293T cells (3.5 ϫ 10 6 cells) were transfected with 2.5 g of Myc-CoREST1, MycCoREST2, or Myc-CoREST3 and harvested 48 h after transfection. Coimmunoprecipitation assays and Western blot assays were carried out as described previously (11). To quantify the amount of coprecipitated proteins (HDACs and LSD1/KDM1A), specific bands of Western blots were quantified with ImageJ software, and values were corrected by the relative amount of each Myc-CoREST protein precipitated.…”

Section: Animalsmentioning

confidence: 99%

“…For instance, in hematopoietic cells, the zinc finger transcription factor Gfi (growth factor independent) recruits CoREST to regulate the expression of target genes during erythroid differentiation (9,10). CoREST also controls the expression of certain genes during physiopathological processes, as exemplified by its participation in repressing the heat shock (11) and proinflammatory (12) responses.…”

mentioning

confidence: 99%

Differential Properties of Transcriptional Complexes Formed by the CoREST Family

Barrios

Gómez

Sáez

et al. 2014

Molecular and Cellular Biology

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dMammalian genomes harbor three CoREST genes. rcor1 encodes CoREST (CoREST1), and the paralogues rcor2 and rcor3 encode CoREST2 and CoREST3, respectively. Here, we describe specific properties of transcriptional complexes formed by CoREST proteins with the histone demethylase LSD1/KDM1A and histone deacetylases 1 and 2 (HDAC1/2) and the finding that all three CoRESTs are expressed in the adult rat brain. CoRESTs interact equally strongly with LSD1/KDM1A. Structural analysis shows that the overall conformation of CoREST3 is similar to that of CoREST1 complexed with LSD1/KDM1A. Nonetheless, transcriptional repressive capacity of CoREST3 is lower than that of CoREST1, which correlates with the observation that CoREST3 leads to a reduced LSD1/KDM1A catalytic efficiency. Also, CoREST2 shows a lower transcriptional repression than CoREST1, which is resistant to HDAC inhibitors. CoREST2 displays lower interaction with HDAC1/2, which is barely present in LSD1/KDM1A-CoREST2 complexes. A nonconserved leucine in the first SANT domain of CoREST2 severely weakens its association with HDAC1/2. Furthermore, CoREST2 mutants with increased HDAC1/2 interaction and those without HDAC1/2 interaction exhibit equivalent transcriptional repression capacities, indicating that CoREST2 represses in an HDAC-independent manner. In conclusion, differences among CoREST proteins are instrumental in the modulation of protein-protein interactions and catalytic activities of LSD1/KDM1A-CoREST-HDAC complexes, fine-tuning gene expression regulation.

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“…Recently, an interaction between HSF1 and HDAC1/2 was reported in the repression of estrogen-dependent transcription by heregulin (Khaleque et al, 2007). Moreover the protein CoREST, which belongs to HDAC1 and 2 repressor complexes, has recently been implicated in the control of hsp70 expression in non-heat-shocked and heat-shocked cells (Gó mez et al, 2008). Our study explores a totally new aspect of the heatshock response and identifies HDAC1 and 2 as important general regulators of genome wide organization in heatshocked cells, regulating the heat-induced epigenetic changes.…”

Section: Stress and Modification Of The Histone Codementioning

confidence: 99%

Heat-Shock Factor 1 Controls Genome-wide Acetylation in Heat-shocked Cells

Fritah

Col

Boyault

et al. 2009

MBoC

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A major regulatory function has been evidenced here for HSF1, the key transcription factor of the heat-shock response, in a large-scale remodeling of the cell epigenome. Indeed, upon heat shock, HSF1, in addition to its well-known transactivating activities, mediates a genome-wide and massive histone deacetylation. Investigating the underlying mechanisms, we show that HSF1 specifically associates with and uses HDAC1 and HDAC2 to trigger this heat-shock-dependent histone deacetylation. This work therefore identifies HSF1 as a master regulator of global chromatin acetylation and reveals a cross-talk between HSF1 and histone deacetylases in the general control of genome organization in response to heat shock. INTRODUCTIONExposure of cells to environmental stress conditions results in the inducible expression of a family of proteins termed heat-shock proteins (HSPs) whose function is to protect the cells from stress-induced damages (reviewed in Lindquist¤ 1986;Christians et al., 2002). In parallel, heat shock also induces a global down-regulation of non-heat-shocked genes (Spradling et al., 1975;Jamrich et al., 1977;Findly and Pederson, 1981;Higashikubo and Roti Roti, 1993). Heatshock transcription factor 1 (HSF1) is responsible for the stress-induced activation of heat-shock genes and chromatin remodeling events associated with HSF1-mediated gene activation has been thoroughly investigated in the literature (reviewed in Wu, 1995;Sorger, 1991;Morimoto et al., 1992Morimoto et al., , 1996. In contrast, mechanisms underlying gene repression have been investigated to much lesser extent.In eukaryotic cells, the packaging of DNA into chromatin provides a dynamic structure for controlling transcription. The fundamental unit of chromatin structure, the nucleosome, is formed by a 147-base pair DNA fragment wrapped around an octamer of the four types of histones: H2A, H2B, H3 and H4, with N-terminal tails protruding from the nucleosome. Posttranslational modifications of histone tails are known to be associated with differences in gene expression (reviewed in Jenuwein and Allis, 2001;Mellor, 2006). Among other modifications, acetylation is considered as a key player in the epigenetic control of gene expression and is associated to transcriptionally active regions (reviewed in Cheung et al., 2000). The balance between opposite enzymatic activities, histone acetyl transferases (HATs), and histone deacetylases (HDACs), directly controls the level of histone acetylation and potent inhibitors of histone deacetylases, such as trichostatin A (TSA), induce a global hyperacetylation of the chromatin (Yoshida et al., 1990). Different classes of HDACs have been identified so far, with different structures and activities (reviewed in Yang and Seto, 2008). Class I and class II HDACs are classical HDACs whose activity is inhibited by TSA, whereas class III is a family of NADϩ-dependent proteins the activity of which is not affected by TSA. Only one member of class IV HDACs, HDAC11, has been identified so far. Three HDACs of class I, HDAC1...

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CoREST Represses the Heat Shock Response Mediated by HSF1

Cited by 40 publications

References 52 publications

CRF binding protein facilitates the presence of CRF type 2α receptor on the cell surface

CRF binding protein facilitates the presence of CRF type 2α receptor on the cell surface

Differential Properties of Transcriptional Complexes Formed by the CoREST Family

Heat-Shock Factor 1 Controls Genome-wide Acetylation in Heat-shocked Cells

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