Search results for "CHROMATIN"
showing 10 items of 490 documents
Epigenetic Regulation of TRAIL Signaling: Implication for Cancer Therapy
2019
International audience; One of the main characteristics of carcinogenesis relies on genetic alterations in DNA and epigenetic changes in histone and non-histone proteins. At the chromatin level, gene expression is tightly controlled by DNA methyl transferases, histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyl-binding proteins. In particular, the expression level and function of several tumor suppressor genes, or oncogenes such as c-Myc, p53 or TRAIL, have been found to be regulated by acetylation. For example, HATs are a group of enzymes, which are responsible for the acetylation of histone proteins, resulting in chromatin relaxation and transcriptional activation,…
Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements.
2017
Interpretation of variants of uncertain significance, especially chromosomal rearrangements in non-coding regions of the human genome, remains one of the biggest challenges in modern molecular diagnosis. To improve our understanding and interpretation of such variants, we used high-resolution three-dimensional chromosomal structural data and transcriptional regulatory information to predict position effects and their association with pathogenic phenotypes in 17 subjects with apparently balanced chromosomal abnormalities. We found that the rearrangements predict disruption of long-range chromatin interactions between several enhancers and genes whose annotated clinical features are strongly …
Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues.
2016
International audience; Specific gene transcription is a key biological process that underlies cell fate decision during embryonic development. The biological process is mediated by transcription factors which bind genomic regulatory regions including enhancers and promoters of cardiac constitutive genes. DNA is wrapped around histones that are subjected to chemical modifications. Modifications of histones further lead to repressed, activated or poised gene transcription, thus bringing another level of fine tuning regulation of gene transcription. Embryonic Stem cells (ES cells) recapitulate within embryoid bodies (i.e., cell aggregates) or in 2D culture the early steps of cardiac developme…
A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export.
2018
17 páginas, 12 figuras.
CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly
2016
SummaryHuman centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation. Without the continuing presence of CENP-A, CENP-B binding …
Histone Post-Translational Modifications and Nucleosome Organisation in Transcriptional Regulation: Some Open Questions
2017
The organisation of chromatin is first discussed to conclude that nucleosomes play both structural and transcription-regulatory roles. The presence of nucleosomes makes difficult the access of transcriptional factors to their target sequences and the action of RNA polymerases. The histone post-translational modifications and nucleosome remodelling are first discussed, from a historical point of view, as mechanisms to remove the obstacles imposed by chromatin structure to transcription. Instead of reviewing the state of the art of the whole field, this review is centred on some open questions. First, some “non-classical” histone modifications, such as short-chain acylations other than acetyl…
Deep learning architectures for prediction of nucleosome positioning from sequences data
2018
Abstract Background Nucleosomes are DNA-histone complex, each wrapping about 150 pairs of double-stranded DNA. Their function is fundamental for one of the primary functions of Chromatin i.e. packing the DNA into the nucleus of the Eukaryote cells. Several biological studies have shown that the nucleosome positioning influences the regulation of cell type-specific gene activities. Moreover, computational studies have shown evidence of sequence specificity concerning the DNA fragment wrapped into nucleosomes, clearly underlined by the organization of particular DNA substrings. As the main consequence, the identification of nucleosomes on a genomic scale has been successfully performed by com…
Deep learning network for exploiting positional information in nucleosome related sequences
2017
A nucleosome is a DNA-histone complex, wrapping about 150 pairs of double-stranded DNA. The role of nucleosomes is to pack the DNA into the nucleus of the Eukaryote cells to form the Chromatin. Nucleosome positioning genome wide play an important role in the regulation of cell type-specific gene activities. Several biological studies have shown sequence specificity of nucleosome presence, clearly underlined by the organization of precise nucleotides substrings. Taking into consideration such advances, the identification of nucleosomes on a genomic scale has been successfully performed by DNA sequence features representation and classical supervised classification methods such as Support Vec…
Loss of ISWI Function in Drosophila Nuclear Bodies Drives Cytoplasmic Redistribution of Drosophila TDP-43
2018
Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases. Indeed, sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration share as hallmarks ubiquitin-positive inclusions. Recently, the wide spectrum of neurodegenerative diseases characterized by RBPs functions’ alteration and loss was coll…
Differential staining of peripheral nuclear chromatin with Acridine orange implies an A-form epichromatin conformation of the DNA
2018
ABSTRACT The chromatin observed by conventional electron microscopy under the nuclear envelope constitutes a single layer of dense 30–35 nm granules, while ∼30 nm fibrils laterally attached to them, form large patches of lamin-associated domains (LADs). This particular surface “epichromatin” can be discerned by specific (H2A+H2B+DNA) conformational antibody at the inner nuclear envelope and around mitotic chromosomes. In order to differentiate the DNA conformation of the peripheral chromatin we applied an Acridine orange (AO) DNA structural test involving RNAse treatment and the addition of AO after acid pre-treatment. MCF-7 cells treated in this way revealed yellow/red patches of LADs atta…