Spatial segregation of heterochromatin: Uncovering functionality in a multicellular organism

Cabianca, Daphne S.; Gasser, Susan M.

doi:10.1080/19491034.2016.1187354

Cited by 20 publications

(12 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the past, several scientists suggested that heterochromatin regulates the differential expression of genes by biophysical mechanisms, by a force field gradient acting in the nucleus space [17][18][19][20][21]. Currently, there are enough results that include those coming from the nucleus image analysis and chromosome conformation capture techniques, which suggests that the heterochromatin mediating the gene silencing position effect is responsible for the differentiation-specific expression of the genetically active euchromatin [22][23][24][25][26][27][28][29][30]. The above evidence suggests that a three-dimensional heterochromatin (3D) topology created by 3D contacts represents a lacking "there", i.e., the positional information of the supra-chromosomal network in the cell nucleus for transcription speciation.…”

Section: Regulation Of the Human Genome: Networking By Self-organisatmentioning

confidence: 99%

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

Ērenpreisa

Giuliani

2019

IJMS

View full text Add to dashboard Cite

The apparent lack of success in curing cancer that was evidenced in the last four decades of molecular medicine indicates the need for a global re-thinking both its nature and the biological approaches that we are taking in its solution. The reductionist, one gene/one protein method that has served us well until now, and that still dominates in biomedicine, requires complementation with a more systemic/holistic approach, to address the huge problem of cross-talk between more than 20,000 protein-coding genes, about 100,000 protein types, and the multiple layers of biological organization. In this perspective, the relationship between the chromatin network organization and gene expression regulation plays a fundamental role. The elucidation of such a relationship requires a non-linear thermodynamics approach to these biological systems. This change of perspective is a necessary step for developing successful 'tumour-reversion' therapeutic strategies.

show abstract

Section: Regulation Of the Human Genome: Networking By Self-organisatmentioning

confidence: 99%

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

Ērenpreisa

Giuliani

2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Eukaryotic chromosomes are subdivided into less condensed euchromatin and more densely packed heterochromatin. The facultative heterochromatin that is dispersed on the chromosome arms (hereafter ChAs) is mostly composed of silent tissue-specific genes and transposable elements (TEs), whereas pericentromeric and telomeric regions highly enriched in satellite DNA, TEs and other repeats form the constitutive heterochromatin (the 2LHet, 2RHet, 3LHet, 3RHet, XHet chromosome regions of dm3/R5 genome assembly; hereafter CHet) (reviewed in [ 1 , 2 ]). Immunostaining and electron microscopy observations indicate that in mammalian cells, both the facultative and constitutive heterochromatin are located close to the nuclear envelope and around the nucleoli, with an interesting exception being the rod photoreceptor cells of animals with nocturnal vision, where the heterochromatin is centrally positioned ([ 3 ] and references therein).…”

Section: Introductionmentioning

confidence: 99%

The large fraction of heterochromatin in Drosophila neurons is bound by both B-type lamin and HP1a

Pindyurin

Ilyin

Ivankin

et al. 2018

Epigenetics & Chromatin

View full text Add to dashboard Cite

BackgroundIn most mammalian cell lines, chromatin located at the nuclear periphery is represented by condensed heterochromatin, as evidenced by microscopy observations and DamID mapping of lamina-associated domains (LADs) enriched in dimethylated Lys9 of histone H3 (H3K9me2). However, in Kc167 cell culture, the only Drosophilla cell type where LADs have previously been mapped, they are neither H3K9me2-enriched nor overlapped with the domains of heterochromatin protein 1a (HP1a).ResultsHere, using cell type-specific DamID we mapped genome-wide LADs, HP1a and Polycomb (Pc) domains from the central brain, Repo-positive glia, Elav-positive neurons and the fat body of Drosophila third instar larvae. Strikingly, contrary to Kc167 cells of embryonic origin, in neurons and, to a lesser extent, in glia and the fat body, HP1a domains appear to overlap strongly with LADs in both the chromosome arms and pericentromeric regions. Accordingly, centromeres reside closer to the nuclear lamina in neurons than in Kc167 cells. As expected, active gene promoters are mostly not present in LADs, HP1a and Pc domains. These domains are occupied by silent or weakly expressed genes with genes residing in the HP1a-bound LADs expressed at the lowest level.ConclusionsIn various differentiated Drosophila cell types, we discovered the existence of peripheral heterochromatin, similar to that observed in mammals. Our findings support the model that peripheral heterochromatin matures enhancing the repression of unwanted genes as cells terminally differentiate.Electronic supplementary materialThe online version of this article (10.1186/s13072-018-0235-8) contains supplementary material, which is available to authorized users.

show abstract

“…For example, in humans, regions of constitutive heterochromatin are typically enriched for H3K9 trimethylation, whereas regions of facultative heterochromatin such as those found in inactivated X chromosomes and at loci that regulate cell identity are typically enriched for H3K27 trimethylation (1,2). Despite the range of mechanisms and proteins involved in heterochromatin formation and maintenance, certain characteristics appear universal and underlie a fundamental relationship between heterochromatin structure and function: Heterochromatin is structurally compact, localizes to distinct areas of the nucleus, and promotes transcriptional repression by limiting access of RNA polymerases to DNA (3)(4)(5)(6)(7)(8)(9)(10). The replication and epigenetic inheritance of heterochromatin are enigmatic in at least three ways.…”

mentioning

confidence: 99%

Pivotal roles of PCNA loading and unloading in heterochromatin function

Janke

King

Kupiec

et al. 2018

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

View full text Add to dashboard Cite

In , heterochromatin structures required for transcriptional silencing of the and loci are duplicated in coordination with passing DNA replication forks. Despite major reorganization of chromatin structure, the heterochromatic, transcriptionally silent states of and are successfully maintained throughout S-phase. Mutations of specific components of the replisome diminish the capacity to maintain silencing of and through replication. Similarly, mutations in histone chaperones involved in replication-coupled nucleosome assembly reduce gene silencing. Bridging these observations, we determined that the proliferating cell nuclear antigen (PCNA) unloading activity of Elg1 was important for coordinating DNA replication forks with the process of replication-coupled nucleosome assembly to maintain silencing of and through S-phase. Collectively, these data identified a mechanism by which chromatin reassembly is coordinated with DNA replication to maintain silencing through S-phase.

show abstract

Spatial segregation of heterochromatin: Uncovering functionality in a multicellular organism

Cited by 20 publications

References 34 publications

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

The large fraction of heterochromatin in Drosophila neurons is bound by both B-type lamin and HP1a

Pivotal roles of PCNA loading and unloading in heterochromatin function

Contact Info

Product

Resources

About