scholarly journals Cyto-nuclear shuttling of afadin is required for rapid estradiol-mediated modifications of histone H3

2018 ◽  
Author(s):  
Katherine J. Sellers ◽  
Iain A. Watson ◽  
Deepak P. Srivastava
Keyword(s):  
Learning And Memory ◽  
Transcriptional Activation ◽  
Histone H3 ◽  
Neuronal Population ◽  
Nuclear Accumulation ◽  
Estradiol Treatment ◽  
Nuclear Trafficking ◽  
17Β Estradiol ◽  
Nuclear Shuttling ◽  
And Function

AbstractEstrogens have been shown to rapidly regulate local signalling events at both synapses and within the nucleus. The result of these signalling events is to rapidly modulate synapse structure and function, as well as epigenetic mechanisms including histone modifications. Ultimately these mechanisms are thought to contribute to long-lasting changes in neural circuitry, and thus influences cognitive functions such as learning and memory. However, the mechanisms by which estrogen-mediated local synaptic and nuclear signalling events are coordinated are not well understood. In this study we have found that the scaffold protein afadin, (also known as AF-6), undergoes a bi-directional trafficking to both synaptic and nuclear compartment in response to acute 17β-estradiol (estradiol) treatment. Interestingly, nuclear accumulation of afadin was coincidental with an increase in the phosphorylation of histone H3 at serine 10 (H3S10p). This histone modification is associated with the remodelling of chromatin into an open euchromatin state, allowing for transcriptional activation and related learning and memory processes. Critically, the cyto-nuclear trafficking of afadin was required for estradiol-dependent H3S10p. We further determined that nuclear accumulation of afadin is sufficient to induce phosphorylation of the mitogentic kinases ERK1/2 (pERK1/2) within the nucleus. Moreover, nuclear pERK1/2 was required for estradiol-dependent H3S10p. Taken together, we propose a model whereby estradiol incudes the bi-directional trafficking of afadin to synaptic and nuclear sub-compartments. Within the nucleus, afadin is required for increased pERK1/2 which in turn is required for H3S10p. Therefore this represents a mechanism through which estrogens may be able to coordinate both synaptic and nucleosomal events within the same neuronal population.

scholarly journals In Vivo 17β-Estradiol Treatment Contributes to Podocyte Actin Stabilization in Female db/db Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (12) ◽  
pp. 5888-5895 ◽  
Author(s):  
Paola Catanuto ◽  
Alessia Fornoni ◽  
Simone Pereira-Simon ◽  
Fayi Wu ◽  
Kerry L. Burnstein ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Transcriptional Activation ◽  
Cell Types ◽  
Proper Function ◽  
Estradiol Treatment ◽  
Diabetic Glomerulosclerosis ◽  
Podocyte Damage ◽  
Rac1 Activity ◽  
17Β Estradiol

Abstract We recently showed that 17β-estradiol (E2) treatment ameliorated type 2 diabetic glomerulosclerosis in mice in part by protecting podocyte structure and function. Progressive podocyte damage is characterized by foot process effacement, vacuolization, detachment of podocytes from the glomerular basement membrane, and apoptosis. In addition, podocytes are highly dependent on the preservation of their actin cytoskeleton to ensure proper function and survival. Because E2 administration prevented podocyte damage in our study on diabetic db/db mice and has been shown to regulate both actin cytoskeleton and apoptosis in other cell types and tissues, we investigated whether actin remodeling and apoptosis were prevented in podocytes isolated from E2-treated diabetic db/db mice. We performed G-actin/F-actin assays, Western analysis for Hsp25 expression, Ras-related C3 botulinum toxin substrate 1 (Rac1) activity, and apoptosis assays on previously characterized podocytes isolated from both in vivo-treated placebo and E2 female db/db mice. We found that in vivo E2 protects against a phenotype change in the cultured podocytes characterized by a percent increase of F-actin vs. G-actin, suppression of Hsp25 expression and transcriptional activation, increase of Rac1 activity, and decreased apoptotic intermediates. We conclude from these studies that E2 treatment protects against podocyte damage and may prevent/reduce diabetes-induced kidney disease.

scholarly journals Local Regulation and Function of Importin-β1 During Transcription-Dependent Plasticity

2020 ◽  
Author(s):  
Yan Jun Lee ◽  
Sheeja Navakkode ◽  
Chee Fan Tan ◽  
Siu Kwan Sze ◽  
Sreedharan Sajikumar ◽  
...  
Keyword(s):  
Nuclear Import ◽  
Nuclear Accumulation ◽  
Nuclear Entry ◽  
Local Protein Synthesis ◽  
Show Evidence ◽  
Nuclear Shuttling ◽  
And Function ◽  
Activity Dependent

SUMMARYActivity-dependent transcription is critical for the encoding of long-term memories. Regulated nuclear entry of soluble proteins is one method to relay synaptic signals to the nucleus to couple neuronal excitation with transcription. To date, the role of importin-β1 in nuclear shuttling of proteins during activity-dependent transcription has always been inferred but not directly investigated. In this study, we demonstrate activity-dependent nuclear accumulation of importin-β1 from the soma and the synapto-dendritic compartments. Importantly, inhibition of importin-β1 mediated nuclear import during synaptic stimulation impairs long-term plasticity. We show evidence that importin-β1 mRNA-ribosome complex is distributed throughout the synapto-dendritic compartment and synaptic stimulation induces importin-β1 local protein synthesis. Finally, we identified candidate proteins that associate with importin-β1 at the synapse and characterize NDRG1 as an importin-β1 interactor that undergoes activitydependent translocation into the nucleus. Collectively, our results highlight the crucial role of importin-β1 in nuclear import of proteins during long-term plasticity.

scholarly journals Spanning the gap: unraveling RSC dynamics in vivo

2021 ◽  
Author(s):  
Heinz Neumann ◽  
Bryan J. Wilkins
Keyword(s):  
Cell Cycle ◽  
Posttranslational Modifications ◽  
Transcriptional Activation ◽  
Binding Mode ◽  
Binding Modes ◽  
Binding Domains ◽  
Binding Interface ◽  
The Many ◽  
And Function

AbstractMultiple reports over the past 2 years have provided the first complete structural analyses for the essential yeast chromatin remodeler, RSC, providing elaborate molecular details for its engagement with the nucleosome. However, there still remain gaps in resolution, particularly within the many RSC subunits that harbor histone binding domains.Solving contacts at these interfaces is crucial because they are regulated by posttranslational modifications that control remodeler binding modes and function. Modifications are dynamic in nature often corresponding to transcriptional activation states and cell cycle stage, highlighting not only a need for enriched spatial resolution but also temporal understanding of remodeler engagement with the nucleosome. Our recent work sheds light on some of those gaps by exploring the binding interface between the RSC catalytic motor protein, Sth1, and the nucleosome, in the living nucleus. Using genetically encoded photo-activatable amino acids incorporated into histones of living yeast we are able to monitor the nucleosomal binding of RSC, emphasizing the regulatory roles of histone modifications in a spatiotemporal manner. We observe that RSC prefers to bind H2B SUMOylated nucleosomes in vivo and interacts with neighboring nucleosomes via H3K14ac. Additionally, we establish that RSC is constitutively bound to the nucleosome and is not ejected during mitotic chromatin compaction but alters its binding mode as it progresses through the cell cycle. Our data offer a renewed perspective on RSC mechanics under true physiological conditions.

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.

Histone H3 transcription in Saccharomyces cerevisiae is controlled by multiple cell cycle activation sites and a constitutive negative regulatory element

1992 ◽  
Vol 12 (12) ◽  
pp. 5455-5463 ◽  
Author(s):  
K B Freeman ◽  
L R Karns ◽  
K A Lutz ◽  
M M Smith
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Division ◽  
Transcriptional Activation ◽  
Regulatory Element ◽  
Histone H3 ◽  
Regulatory Elements ◽  
Cell Division Cycle ◽  
Cell Cycle Activation ◽  
Multiple Cell

The promoters of the Saccharomyces cerevisiae histone H3 and H4 genes were examined for cis-acting DNA sequence elements regulating transcription and cell division cycle control. Deletion and linker disruption mutations identified two classes of regulatory elements: multiple cell cycle activation (CCA) sites and a negative regulatory site (NRS). Duplicate 19-bp CCA sites are present in both the copy I and copy II histone H3-H4 promoters arranged as inverted repeats separated by 45 and 68 bp. The CCA sites are both necessary and sufficient to activate transcription under cell division cycle control. A single CCA site provides cell cycle control but is a weak transcriptional activator, while an inverted repeat comprising two CCA sites provides both strong transcriptional activation and cell division cycle control. The NRS was identified in the copy I histone H3-H4 promoter. Deletion or disruption of the NRS increased the level of the histone H3 promoter activity but did not alter the cell division cycle periodicity of transcription. When the CCA sites were deleted from the histone promoter, the NRS element was unable to confer cell division cycle control on the remaining basal level of transcription. When the NRS element was inserted into the promoter of a foreign reporter gene, transcription was constitutively repressed and did not acquire cell cycle regulation.

scholarly journals Transcriptional Activation of Deoxyribonucleic Acid Polymerase α Gene Expression in MCF-7 Cells by 17β-Estradiol*

Endocrinology ◽  
2001 ◽  
Vol 142 (3) ◽  
pp. 1000-1008 ◽  
Author(s):  
Ismael Samudio ◽  
Carrie Vyhlidal ◽  
Fan Wang ◽  
Matthew Stoner ◽  
Ichen Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Deoxyribonucleic Acid ◽  
17Β Estradiol ◽  
Mcf 7

scholarly journals Reading and Function of a Histone Code Involved in Targeting Corepressor Complexes for Repression

2005 ◽  
Vol 25 (1) ◽  
pp. 324-335 ◽  
Author(s):  
Ho-Geun Yoon ◽  
Youngsok Choi ◽  
Philip A. Cole ◽  
Jiemin Wong
Keyword(s):  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Hormone Receptors ◽  
Critical Role ◽  
Pericentric Heterochromatin ◽  
Histone Code ◽  
Stable Association ◽  
And Function

ABSTRACT A central question in histone code theory is how various codes are recognized and utilized in vivo. Here we show that TBL1 and TBLR1, two WD-40 repeat proteins in the corepressor SMRT/N-CoR complexes, are functionally redundant and essential for transcriptional repression by unliganded thyroid hormone receptors (TR) but not essential for transcriptional activation by liganded TR. TBL1 and TBLR1 bind preferentially to hypoacetylated histones H2B and H4 in vitro and have a critical role in targeting the corepressor complexes to chromatin in vivo. We show that targeting SMRT/N-CoR complexes to the deiodinase 1 gene (D1) requires at least two interactions, one between unliganded TR and SMRT/N-CoR and the other between TBL1/TBLR1 and hypoacetylated histones. Neither interaction alone is sufficient for the stable association of the corepressor complexes with the D1 promoter. Our data support a feed-forward working model in which deacetylation exerted by initial unstable recruitment of SMRT/N-CoR complexes via their interaction with unliganded TR generates a histone code that serves to stabilize their own recruitment. Similarly, we find that targeting of the Sin3 complex to pericentric heterochromatin may also follow this model. Our studies provide an in vivo example that a histone code is not read independently but is recognized in the context of other interactions.

scholarly journals Relationship of Depression and function of Attention, Planning and Verbal Learning and Memory

2019 ◽  
Vol 8 (9) ◽  
pp. 214-225
Author(s):  
Nongmeikapam Premika Devi
Keyword(s):  
Learning And Memory ◽  
Verbal Learning ◽  
Education Level ◽  
Auditory Verbal Learning ◽  
And Function ◽  
Age Range ◽  
Relationship Of ◽  
The Relationship ◽  
Minimum Education ◽  
Hiv Aids

The present study examines the relationship of depression and the neuropsychologicalfunction of attention, planning and auditory verbal learning and memory among individualswith HIV/AIDS. 200 subjects who were HIV/AIDS positive (100 males and 100 females) andwere within age range of 20 to 50 years and minimum education level of 8th standard weretaken. The result indicates that Depression slows down the performance of attention; alsodepression most likely decreases the function of auditory verbal learning and memory

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