Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach.
Three dimensional nuclear architecture is important for genome function, but is still poorly understood. In particular, little is known about the role of the "boundary conditions"--points of attachment between chromosomes and the nuclear envelope. We describe a method for modeling the 3D o...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3961273?pdf=render |
| _version_ | 1811212815554314240 |
|---|---|
| author | Nicholas Allen Kinney Igor V Sharakhov Alexey V Onufriev |
| author_facet | Nicholas Allen Kinney Igor V Sharakhov Alexey V Onufriev |
| author_sort | Nicholas Allen Kinney |
| collection | DOAJ |
| description | Three dimensional nuclear architecture is important for genome function, but is still poorly understood. In particular, little is known about the role of the "boundary conditions"--points of attachment between chromosomes and the nuclear envelope. We describe a method for modeling the 3D organization of the interphase nucleus, and its application to analysis of chromosome-nuclear envelope (Chr-NE) attachments of polytene (giant) chromosomes in Drosophila melanogaster salivary glands. The model represents chromosomes as self-avoiding polymer chains confined within the nucleus; parameters of the model are taken directly from experiment, no fitting parameters are introduced. Methods are developed to objectively quantify chromosome territories and intertwining, which are discussed in the context of corresponding experimental observations. In particular, a mathematically rigorous definition of a territory based on convex hull is proposed. The self-avoiding polymer model is used to re-analyze previous experimental data; the analysis suggests 33 additional Chr-NE attachments in addition to the 15 already explored Chr-NE attachments. Most of these new Chr-NE attachments correspond to intercalary heterochromatin--gene poor, dark staining, late replicating regions of the genome; however, three correspond to euchromatin--gene rich, light staining, early replicating regions of the genome. The analysis also suggests 5 regions of anti-contact, characterized by aversion for the NE, only two of these correspond to euchromatin. This composition of chromatin suggests that heterochromatin may not be necessary or sufficient for the formation of a Chr-NE attachment. To the extent that the proposed model represents reality, the confinement of the polytene chromosomes in a spherical nucleus alone does not favor the positioning of specific chromosome regions at the NE as seen in experiment; consequently, the 15 experimentally known Chr-NE attachment positions do not appear to arise due to non-specific (entropic) forces. Robustness of the key conclusions to model assumptions is thoroughly checked. |
| first_indexed | 2024-04-12T05:35:34Z |
| format | Article |
| id | doaj.art-62d73bc05e0d421b821a0cdef704694b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:35:34Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-62d73bc05e0d421b821a0cdef704694b2022-12-22T03:45:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9194310.1371/journal.pone.0091943Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach.Nicholas Allen KinneyIgor V SharakhovAlexey V OnufrievThree dimensional nuclear architecture is important for genome function, but is still poorly understood. In particular, little is known about the role of the "boundary conditions"--points of attachment between chromosomes and the nuclear envelope. We describe a method for modeling the 3D organization of the interphase nucleus, and its application to analysis of chromosome-nuclear envelope (Chr-NE) attachments of polytene (giant) chromosomes in Drosophila melanogaster salivary glands. The model represents chromosomes as self-avoiding polymer chains confined within the nucleus; parameters of the model are taken directly from experiment, no fitting parameters are introduced. Methods are developed to objectively quantify chromosome territories and intertwining, which are discussed in the context of corresponding experimental observations. In particular, a mathematically rigorous definition of a territory based on convex hull is proposed. The self-avoiding polymer model is used to re-analyze previous experimental data; the analysis suggests 33 additional Chr-NE attachments in addition to the 15 already explored Chr-NE attachments. Most of these new Chr-NE attachments correspond to intercalary heterochromatin--gene poor, dark staining, late replicating regions of the genome; however, three correspond to euchromatin--gene rich, light staining, early replicating regions of the genome. The analysis also suggests 5 regions of anti-contact, characterized by aversion for the NE, only two of these correspond to euchromatin. This composition of chromatin suggests that heterochromatin may not be necessary or sufficient for the formation of a Chr-NE attachment. To the extent that the proposed model represents reality, the confinement of the polytene chromosomes in a spherical nucleus alone does not favor the positioning of specific chromosome regions at the NE as seen in experiment; consequently, the 15 experimentally known Chr-NE attachment positions do not appear to arise due to non-specific (entropic) forces. Robustness of the key conclusions to model assumptions is thoroughly checked.http://europepmc.org/articles/PMC3961273?pdf=render |
| spellingShingle | Nicholas Allen Kinney Igor V Sharakhov Alexey V Onufriev Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. PLoS ONE |
| title | Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. |
| title_full | Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. |
| title_fullStr | Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. |
| title_full_unstemmed | Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. |
| title_short | Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. |
| title_sort | investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly a model based approach |
| url | http://europepmc.org/articles/PMC3961273?pdf=render |
| work_keys_str_mv | AT nicholasallenkinney investigationofthechromosomeregionswithsignificantaffinityforthenuclearenvelopeinfruitflyamodelbasedapproach AT igorvsharakhov investigationofthechromosomeregionswithsignificantaffinityforthenuclearenvelopeinfruitflyamodelbasedapproach AT alexeyvonufriev investigationofthechromosomeregionswithsignificantaffinityforthenuclearenvelopeinfruitflyamodelbasedapproach |