Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2
The induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that the removal of the special AT-rich binding protein 2 (SATB2), a nuclear pro...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/6/966 |
| _version_ | 1827649656999378944 |
|---|---|
| author | Ryan A. V. Bell Mohammad H. Al-Khalaf Steve Brunette Dalal Alsowaida Alphonse Chu Hina Bandukwala Georg Dechant Galina Apostolova F. Jeffrey Dilworth Lynn A. Megeney |
| author_facet | Ryan A. V. Bell Mohammad H. Al-Khalaf Steve Brunette Dalal Alsowaida Alphonse Chu Hina Bandukwala Georg Dechant Galina Apostolova F. Jeffrey Dilworth Lynn A. Megeney |
| author_sort | Ryan A. V. Bell |
| collection | DOAJ |
| description | The induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that the removal of the special AT-rich binding protein 2 (SATB2), a nuclear protein known to bind matrix attachment regions, is a key event in initiating myogenic differentiation. The deletion of myoblast SATB2 in vitro initiates chromatin remodeling and accelerates differentiation, which is dependent on the caspase 7-mediated cleavage of SATB2. A genome-wide analysis indicates that SATB2 binding within chromatin loops and near anchor points influences both loop and sub-TAD domain formation. Consequently, the chromatin changes that occur with the removal of SATB2 lead to the derepression of differentiation-inducing factors while also limiting the expression of genes that inhibit this cell fate change. Taken together, this study demonstrates that the temporal control of the SATB2 protein is critical in shaping the chromatin environment and coordinating the myogenic differentiation program. |
| first_indexed | 2024-03-09T20:00:48Z |
| format | Article |
| id | doaj.art-401e503390fc466fa68ff97a37303090 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:00:48Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-401e503390fc466fa68ff97a373030902023-11-24T00:43:58ZengMDPI AGCells2073-44092022-03-0111696610.3390/cells11060966Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2Ryan A. V. Bell0Mohammad H. Al-Khalaf1Steve Brunette2Dalal Alsowaida3Alphonse Chu4Hina Bandukwala5Georg Dechant6Galina Apostolova7F. Jeffrey Dilworth8Lynn A. Megeney9Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaRegenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaRegenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaRegenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaRegenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaRegenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaInstitute of Neuroscience, Medical University of Innsbruck, A-6020 Innsbruck, AustriaInstitute of Neuroscience, Medical University of Innsbruck, A-6020 Innsbruck, AustriaRegenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaRegenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaThe induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that the removal of the special AT-rich binding protein 2 (SATB2), a nuclear protein known to bind matrix attachment regions, is a key event in initiating myogenic differentiation. The deletion of myoblast SATB2 in vitro initiates chromatin remodeling and accelerates differentiation, which is dependent on the caspase 7-mediated cleavage of SATB2. A genome-wide analysis indicates that SATB2 binding within chromatin loops and near anchor points influences both loop and sub-TAD domain formation. Consequently, the chromatin changes that occur with the removal of SATB2 lead to the derepression of differentiation-inducing factors while also limiting the expression of genes that inhibit this cell fate change. Taken together, this study demonstrates that the temporal control of the SATB2 protein is critical in shaping the chromatin environment and coordinating the myogenic differentiation program.https://www.mdpi.com/2073-4409/11/6/966SATB2chromatin remodelingcaspase 7myogenic differentiation |
| spellingShingle | Ryan A. V. Bell Mohammad H. Al-Khalaf Steve Brunette Dalal Alsowaida Alphonse Chu Hina Bandukwala Georg Dechant Galina Apostolova F. Jeffrey Dilworth Lynn A. Megeney Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2 Cells SATB2 chromatin remodeling caspase 7 myogenic differentiation |
| title | Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2 |
| title_full | Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2 |
| title_fullStr | Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2 |
| title_full_unstemmed | Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2 |
| title_short | Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2 |
| title_sort | chromatin reorganization during myoblast differentiation involves the caspase dependent removal of satb2 |
| topic | SATB2 chromatin remodeling caspase 7 myogenic differentiation |
| url | https://www.mdpi.com/2073-4409/11/6/966 |
| work_keys_str_mv | AT ryanavbell chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT mohammadhalkhalaf chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT stevebrunette chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT dalalalsowaida chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT alphonsechu chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT hinabandukwala chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT georgdechant chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT galinaapostolova chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT fjeffreydilworth chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 AT lynnamegeney chromatinreorganizationduringmyoblastdifferentiationinvolvesthecaspasedependentremovalofsatb2 |