A possible role of repressive chromatin marks in GLT-1 unresponsivity to dexamethasone in rat cerebellar astrocytes

2011 ◽  
Vol 44 (06) ◽  
Author(s):  
T Perisic ◽  
J Zschocke ◽  
T Rein
2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Mauricio Olguín-Albuerne ◽  
Guadalupe Domínguez ◽  
Julio Morán

Cell death implies morphological changes that may contribute to the progression of this process. In astrocytes, the mechanisms involving the cytoskeletal changes during cell death are not well explored. Although NADPH oxidase (NOX) has been described as being a critical factor in the production of ROS, not much information is available about the participation of NOX-derived ROS in the cell death of astrocytes and their role in the alterations of the cytoskeleton during the death of astrocytes. In this study, we have evaluated the participation of ROS in the death of cultured cerebellar astrocytes using staurosporine (St) as death inductor. We found that astrocytes express NOX1, NOX2, and NOX4. Also, St induced an early ROS production and NOX activation that participate in the death of astrocytes. These findings suggest that ROS produced by St is generated through NOX1 and NOX4. Finally, we showed that the reorganization of tubulin and actin induced by St is ROS independent and that St did not change the level of expression of these cytoskeletal proteins. We conclude that ROS produced by a NOX is required for cell death in astrocytes, but not for the morphological alterations induced by St.


2020 ◽  
Author(s):  
Cristiana Bersaglieri ◽  
Jelena Kresoja-Rakic ◽  
Shivani Gupta ◽  
Dominik Bär ◽  
Rostyslav Kuzyakiv ◽  
...  

AbstractEukaryotic chromosomes are folded into hierarchical domains, enabling the organization of the genome into functional compartments. Nuclear periphery and nucleolus are two nuclear landmarks thought to contribute to repressive chromosome architecture. However, while the role of nuclear lamina (NL) in genome organization has been well documented, the function of the nucleolus remains under-investigated due to the lack of methods for genome-wide maps of nucleolar associated domains (NADs). Here we established a method based on a Dam-fused engineered nucleolar histone H2B that marks DNA contacting the nucleolus. NAD-maps of ESCs and neural progenitors revealed layers of genome compartmentalization with distinct, repressive chromatin states based on the interaction with the nucleolus, NL, or both. NADs showed higher H3K9me2 and lower H3K27me3 content than regions exclusively interacting with NL. Upon ESC differentiation, chromosomes around the nucleolus acquire a more compact, rigid architecture whereas NADs specific for ESCs decrease their interaction strength within the repressive B-compartment strength, unlocking neural genes from repressive nuclear environment. The methodologies here developed will make possible to include the contribution of the nucleolus in future studies investigating the relationship between nuclear space and genome function.


PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0132263 ◽  
Author(s):  
Sheng-Chun Chiu ◽  
Yu-Jou Lin ◽  
Sung-Ying Huang ◽  
Chih-Feng Lien ◽  
Shee-Ping Chen ◽  
...  

2017 ◽  
Author(s):  
Taylor J.R. Penke ◽  
Daniel J. McKay ◽  
Brian D. Strahl ◽  
A. Gregory Matera ◽  
Robert J. Duronio

ABSTRACTHistone post-translational modifications (PTMs) and differential incorporation of variant and canonical histones into chromatin are central modes of epigenetic regulation. Despite similar protein sequences, histone variants are enriched for different suites of PTMs compared to their canonical counterparts. For example, variant histone H3.3 occurs primarily in transcribed regions and is enriched for “active” histone PTMs like Lys9 acetylation (H3.3K9ac), whereas the canonical histone H3 is enriched for Lys9 methylation (H3K9me), which is found in transcriptionally silent heterochromatin. To determine the functions of K9 modification on variant versus canonical H3, we compared the phenotypes caused by engineering H3.3K9R and H3K9R mutant genotypes in Drosophila melanogaster. Whereas most H3.3K9R and a small number of H3K9R mutant animals are capable of completing development and do not have substantially altered protein coding transcriptomes, all H3.3K9RH3K9R combined mutants die soon after embryogenesis and display decreased expression of genes enriched for K9ac. These data suggest that the role of K9ac in gene activation during development can be provided by either H3 or H3.3. Conversely, we found that H3.3K9 is methylated at telomeric transposons, and this mark contributes to repressive chromatin architecture, supporting a role for H3.3 in heterochromatin that is distinct from that of H3. Thus, our genetic and molecular analyses demonstrate that K9 modification of variant and canonical H3 have overlapping roles in development and transcriptional regulation, though to differing extents in euchromatin and heterochromatin.


2018 ◽  
Author(s):  
Christ Leemans ◽  
Marloes van der Zwalm ◽  
Laura Brueckner ◽  
Federico Comoglio ◽  
Tom van Schaik ◽  
...  

AbstractIt is largely unclear whether genes that are naturally embedded in lamina associated domains (LADs) are inactive due to their chromatin environment, or whether LADs are merely secondary to the lack of transcription. We show that hundreds of human promoters become active when moved from their native LAD position to a neutral context in the same cells, indicating that LADs form a repressive environment. Another set of promoters inside LADs is able to "escape" repression, although their transcription elongation is attenuated. By inserting reporters into thousands of genomic locations, we demonstrate that these escaper promoters are intrinsically less sensitive to LAD repression. This is not simply explained by promoter strength, but by the interplay between promoter sequence and local chromatin features that vary strongly across LADs. Enhancers also differ in their sensitivity to LAD chromatin. This work provides a general framework for the systematic understanding of gene regulation by repressive chromatin.HighlightsTwo promoter transplantation strategies elucidate the regulatory role of LAD chromatinLADs are generally repressive, but also highly heterogeneousLADs can impede both promoter activity and transcription elongationPromoters vary intrinsically in their sensitivity to LAD repression


2015 ◽  
Vol 26 (14) ◽  
pp. 2685-2697 ◽  
Author(s):  
Xiaobin Zheng ◽  
Youngjo Kim ◽  
Yixian Zheng

Lamins, the major structural components of the nuclear lamina (NL) found beneath the nuclear envelope, are known to interact with most of the nuclear peripheral chromatin in metazoan cells. Although NL–chromatin associations correlate with a repressive chromatin state, the role of lamins in tethering chromatin to NL and how such tether influences gene expression have remained challenging to decipher. Studies suggest that NL proteins regulate chromatin in a context-dependent manner. Therefore understanding the context of chromatin states based on genomic features, including chromatin–NL interactions, is important to the study of lamins and other NL proteins. By modeling genome organization based on combinatorial patterns of chromatin association with lamin B1, core histone modification, and core and linker histone occupancy, we report six distinct large chromatin landscapes, referred to as histone lamin landscapes (HiLands)-red (R), -orange (O), -yellow (Y), -green (G), -blue (B), and -purple (P), in mouse embryonic stem cells (mESCs). This HiLands model demarcates the previously mapped lamin-associated chromatin domains (LADs) into two HiLands, HiLands-B and HiLands-P, which are similar to facultative and constitutive heterochromatins, respectively. Deletion of B-type lamins in mESCs caused a reduced interaction between regions of HiLands-B and NL as measured by emerin–chromatin interaction. Our findings reveal the importance of analyzing specific chromatin types when studying the function of NL proteins in chromatin tether and regulation.


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