Repeat DNA methylation is modulated by adherens junction signaling
Abstract Through its involvement in gene transcription and heterochromatin formation, DNA methylation regulates how cells interact with their environment. Nevertheless, the extracellular signaling cues that modulate the distribution of this central chromatin modification are largely unclear. DNA met...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-05990-4 |
| _version_ | 1797266657589067776 |
|---|---|
| author | Lisa-Marie Brenner Florian Meyer Haiqian Yang Anja R. Köhler Pavel Bashtrykov Ming Guo Albert Jeltsch Cristiana Lungu Monilola A. Olayioye |
| author_facet | Lisa-Marie Brenner Florian Meyer Haiqian Yang Anja R. Köhler Pavel Bashtrykov Ming Guo Albert Jeltsch Cristiana Lungu Monilola A. Olayioye |
| author_sort | Lisa-Marie Brenner |
| collection | DOAJ |
| description | Abstract Through its involvement in gene transcription and heterochromatin formation, DNA methylation regulates how cells interact with their environment. Nevertheless, the extracellular signaling cues that modulate the distribution of this central chromatin modification are largely unclear. DNA methylation is highly abundant at repetitive elements, but its investigation in live cells has been complicated by methodological challenges. Utilizing a CRISPR/dCas9 biosensor that reads DNA methylation of human α-satellite repeats in live cells, we here uncover a signaling pathway linking the chromatin and transcriptional state of repetitive elements to epithelial adherens junction integrity. Specifically, we find that in confluent breast epithelial cell monolayers, α-satellite repeat methylation is reduced by comparison to low density cultures. This is coupled with increased transcriptional activity at repeats. Through comprehensive perturbation experiments, we identify the junctional protein E-cadherin, which links to the actin cytoskeleton, as a central molecular player for signal relay into the nucleus. Furthermore, we find that this pathway is impaired in cancer cells that lack E-cadherin and are not contact-inhibited. This suggests that the molecular connection between cell density and repetitive element methylation could play a role in the maintenance of epithelial tissue homeostasis. |
| first_indexed | 2024-04-25T01:04:11Z |
| format | Article |
| id | doaj.art-bbb4873ca04d44eeab9819190a7f92a3 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-25T01:04:11Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-bbb4873ca04d44eeab9819190a7f92a32024-03-10T12:19:56ZengNature PortfolioCommunications Biology2399-36422024-03-017111110.1038/s42003-024-05990-4Repeat DNA methylation is modulated by adherens junction signalingLisa-Marie Brenner0Florian Meyer1Haiqian Yang2Anja R. Köhler3Pavel Bashtrykov4Ming Guo5Albert Jeltsch6Cristiana Lungu7Monilola A. Olayioye8Institute of Cell Biology and Immunology, University of StuttgartInstitute of Cell Biology and Immunology, University of StuttgartDepartment of Mechanical Engineering, Massachusetts Institute of TechnologyInstitute of Biochemistry and Technical Biochemistry, University of StuttgartInstitute of Biochemistry and Technical Biochemistry, University of StuttgartDepartment of Mechanical Engineering, Massachusetts Institute of TechnologyInstitute of Biochemistry and Technical Biochemistry, University of StuttgartInstitute of Cell Biology and Immunology, University of StuttgartInstitute of Cell Biology and Immunology, University of StuttgartAbstract Through its involvement in gene transcription and heterochromatin formation, DNA methylation regulates how cells interact with their environment. Nevertheless, the extracellular signaling cues that modulate the distribution of this central chromatin modification are largely unclear. DNA methylation is highly abundant at repetitive elements, but its investigation in live cells has been complicated by methodological challenges. Utilizing a CRISPR/dCas9 biosensor that reads DNA methylation of human α-satellite repeats in live cells, we here uncover a signaling pathway linking the chromatin and transcriptional state of repetitive elements to epithelial adherens junction integrity. Specifically, we find that in confluent breast epithelial cell monolayers, α-satellite repeat methylation is reduced by comparison to low density cultures. This is coupled with increased transcriptional activity at repeats. Through comprehensive perturbation experiments, we identify the junctional protein E-cadherin, which links to the actin cytoskeleton, as a central molecular player for signal relay into the nucleus. Furthermore, we find that this pathway is impaired in cancer cells that lack E-cadherin and are not contact-inhibited. This suggests that the molecular connection between cell density and repetitive element methylation could play a role in the maintenance of epithelial tissue homeostasis.https://doi.org/10.1038/s42003-024-05990-4 |
| spellingShingle | Lisa-Marie Brenner Florian Meyer Haiqian Yang Anja R. Köhler Pavel Bashtrykov Ming Guo Albert Jeltsch Cristiana Lungu Monilola A. Olayioye Repeat DNA methylation is modulated by adherens junction signaling Communications Biology |
| title | Repeat DNA methylation is modulated by adherens junction signaling |
| title_full | Repeat DNA methylation is modulated by adherens junction signaling |
| title_fullStr | Repeat DNA methylation is modulated by adherens junction signaling |
| title_full_unstemmed | Repeat DNA methylation is modulated by adherens junction signaling |
| title_short | Repeat DNA methylation is modulated by adherens junction signaling |
| title_sort | repeat dna methylation is modulated by adherens junction signaling |
| url | https://doi.org/10.1038/s42003-024-05990-4 |
| work_keys_str_mv | AT lisamariebrenner repeatdnamethylationismodulatedbyadherensjunctionsignaling AT florianmeyer repeatdnamethylationismodulatedbyadherensjunctionsignaling AT haiqianyang repeatdnamethylationismodulatedbyadherensjunctionsignaling AT anjarkohler repeatdnamethylationismodulatedbyadherensjunctionsignaling AT pavelbashtrykov repeatdnamethylationismodulatedbyadherensjunctionsignaling AT mingguo repeatdnamethylationismodulatedbyadherensjunctionsignaling AT albertjeltsch repeatdnamethylationismodulatedbyadherensjunctionsignaling AT cristianalungu repeatdnamethylationismodulatedbyadherensjunctionsignaling AT monilolaaolayioye repeatdnamethylationismodulatedbyadherensjunctionsignaling |