The role of chromatin condensation during granulopoiesis in the regulation of gene cluster expression

Stejskal, Stanislav; Koutná, Irena; Matula, Pavel; Ručka, Zdeněk; Daněk, Ondřej; Maška, Martin; Kozubek, Michal

doi:10.4161/epi.5.8.13183

Cited by 6 publications

(5 citation statements)

References 28 publications

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“…Evaluation of the global myogenic cell transcriptome by microarray confirmed the correlation between cell differentiation and the downregulation of gene expression. The same observation was made during granulopoiesis, and it was accompanied by non-random tissue-specific chromatin condensation [32]. We created a chromosome map marking genes with at least a 2-fold change in expression on chromosomes evaluated earlier in 3D FISH experiments.…”

Section: Discussionmentioning

confidence: 83%

Characterisation of Nuclear Architectural Alterations during In Vitro Differentiation of Human Stem Cells of Myogenic Origin

et al. 2013

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Cell differentiation is based on a synchronised orchestra of complex pathways of intrinsic and extrinsic signals that manifest in the induced expression of specific transcription factors and pivotal genes within the nucleus. One cannot ignore the epigenetic status of differentiating cells, comprising not only histones and DNA modifications but also the spatial and temporal intranuclear chromatin organisation, which is an important regulator of nuclear processes. In the present study, we investigated the nuclear architecture of human primary myoblasts and myocytes in an in vitro culture, with reference to global changes in genomic expression. Repositioning of the chromosomal centromeres, along with alterations in the nuclear shape and volume, was observed as a consequence of myotube formation. Moreover, the microarray data showed that during in vitro myogenesis cells tend to silence rather than induce gene expression. The creation of a chromosome map marked with gene expression changes that were at least 2-fold confirmed the observation. Additionally, almost all of the chromosomal centromeres in the differentiated cells preferentially localised near the nuclear periphery when compared to the undifferentiated cells. The exceptions were chromosomes 7 and 11, in which we were unable to confirm the centromere repositioning. In our opinion, this is the first reported observation of the movement of chromosomal centromeres along differentiating myogenic cells. Based on these data we can conclude that the myogenic differentiation with global gene expression changes is accompanied by the spatial repositioning of chromosomes and chromatin remodelling, which are important processes that regulate cell differentiation.

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Section: Discussionmentioning

confidence: 83%

Characterisation of Nuclear Architectural Alterations during In Vitro Differentiation of Human Stem Cells of Myogenic Origin

et al. 2013

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“…Facultative HCh is condensed and transcriptionally inactive, and serves mainly to silence gene expression, as noted in studies of granulopoiesis [102]. Heterochromatization is associated with small RNA molecules and methylated histone H3 sub-types that are recognized by heterochromatin protein 1, a fundamental component of the complex that tightly packages DNA, see review [103].…”

mentioning

confidence: 99%

Environmental and epigenetic effects upon preimplantation embryo metabolism and development

Chason

Csokmay

Segars

et al. 2011

Trends in Endocrinology & Metabolism

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In vitro fertilization has provided a unique window into the metabolic processes that drive embryonic growth and development from a fertilized ovum to a competent blastocyst. Post-fertilization development is dependent upon a dramatic reshuffling of the parental genomes during meiosis, as well as epigenetic changes that provide a new and autonomous set of instructions to guide cellular differentiation both in the embryo and beyond. While early literature focused simply on the substrates and culture conditions required for progress through embryonic development, more recent insights lead us to suggest that the surrounding environment can alter the epigenome, which can, in turn, impact embryonic metabolism and developmental competence.

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“…In fact, we observed changes in nuclear localization in almost all genes that were demonstrated to have altered expression in Mb and Mt. Indeed, many reports have already reported tremendous localization changes of gene position during differentiation of pluripotent stem cells or haematopoietic stem cells 32,33 . Our study, however, is the first to demonstrate this type of regulation in skeletal myoblast terminal differentiation, where the changes are more tenuous and occur in already committed cells.…”

Section: Discussionmentioning

confidence: 64%

Chromatin and transcriptome changes in human myoblasts show spatio-temporal correlations and demonstrate DPP4 inhibition in differentiated myotubes

Kolanowski

Rozwadowska

Zimna

et al. 2020

Sci Rep

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Although less attention was paid to understanding physical localization changes in cell nuclei recently, depicting chromatin interaction maps is a topic of high interest. Here, we focused on defining extensive physical changes in chromatin organization in the process of skeletal myoblast differentiation. Based on RNA profiling data and 3D imaging of myogenic (NCAM1, DES, MYOG, ACTN3, MYF5, MYF6, ACTN2, and MYH2) and other selected genes (HPRT1, CDH15, DPP4 and VCAM1), we observed correlations between the following: (1) expression change and localization, (2) a gene and its genomic neighbourhood expression and (3) intra-chromosome and microscopical locus-centromere distances. In particular, we demonstrated the negative regulation of DPP4 mRnA (p < 0.001) and protein (p < 0.05) in differentiated myotubes, which coincided with a localization change of the DPP4 locus towards the nuclear lamina (p < 0.001) and chromosome 2 centromere (p < 0.001). Furthermore, we discuss the possible role of DPP4 in myoblasts (supported by an inhibition assay). We also provide positive regulation examples (VCAM1 and MYH2). Overall, we describe for the first time existing mechanisms of spatial gene expression regulation in myoblasts that might explain the issue of heterogenic responses observed during muscle regenerative therapies. The changes in the localization of chromosomes and their genes in the three-dimensional nuclear space are tightly regulated but highly variable phenomena. These nuclear interactions have an impact on transcriptional regulation, cell fate and inheritance mechanisms 1-3. Recent years have led to the development of many high-throughput techniques that have vastly increased our knowledge and understanding of chromatin interaction mechanisms 4-7. However, these high-throughput techniques (called '3C techniques') rely on sequence proximity in order to map ongoing interactions. However, creating a physical map of chromatin positioning in relation to the other components of nuclei remains a challenge. To define specific position changes of chromatin in nuclei, microscopic observations of labelled material are necessary, and these techniques have been developed simultaneously with 3C techniques, ultimately combining both approaches 8-12. Human muscle-derived stem cells have been used in regenerative therapies for nearly two decades. Since pluripotent stem cell (iPSC)-based technology is still lacking clinical feasibility, myoblast-based therapies can be considered generally safe and effective for regaining muscle contraction after sphincter rupture or when used in experimental therapies of muscle dystrophies 13. One of the difficulties of cellular therapies is patient variability

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The role of chromatin condensation during granulopoiesis in the regulation of gene cluster expression

Cited by 6 publications

References 28 publications

Characterisation of Nuclear Architectural Alterations during In Vitro Differentiation of Human Stem Cells of Myogenic Origin

Characterisation of Nuclear Architectural Alterations during In Vitro Differentiation of Human Stem Cells of Myogenic Origin

Environmental and epigenetic effects upon preimplantation embryo metabolism and development

Chromatin and transcriptome changes in human myoblasts show spatio-temporal correlations and demonstrate DPP4 inhibition in differentiated myotubes

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