Sin3a is essential for the genome integrity and viability of pluripotent cells

Autor: Jeroen Demmers, David W. M. Tan, Fiona M. Watt, Brian Hendrich, Patrick McDonel
Přispěvatelé: Biochemistry
Rok vydání: 2011
Předmět:
Genome instability
G2 Phase
Male
Pluripotent Stem Cells
Embryonic stem cells
Cell cycle checkpoint
Mice
129 Strain
DNA damage
Cell Survival
Blotting
Western
Apoptosis
Biology
Cell cycle
Genomic Instability
Article
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Mice
0302 clinical medicine
Animals
Induced pluripotent stem cell
E2F
Molecular Biology
Cells
Cultured
030304 developmental biology
Mice
Knockout
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Regulation
Developmental
Cell Biology
Cell Cycle Checkpoints
Embryo
Mammalian
Flow Cytometry
Sin3a
Embryonic stem cell
ICM
3. Good health
Cell biology
E2F Transcription Factors
Mice
Inbred C57BL
Repressor Proteins
Sin3 Histone Deacetylase and Corepressor Complex
Epiblast
Female
030217 neurology & neurosurgery
Germ Layers
Developmental Biology
Zdroj: Developmental Biology
McDonel, P, Demmers, J, Tan, D W M, Watt, F & Hendrich, B D 2012, ' Sin3a is essential for the genome integrity and viability of pluripotent cells ', Developmental Biology, vol. 363, no. 1, pp. 62-73 . https://doi.org/10.1016/j.ydbio.2011.12.019
Developmental Biology, 363(1), 62-73. Elsevier Inc.
ISSN: 1095-564X
0012-1606
Popis: The Sin3a/HDAC co-repressor complex is a critical regulator of transcription networks that govern cell cycle control and apoptosis throughout development. Previous studies have identified Sin3a as essential for embryonic development around the time of implantation, during which the epiblast cell cycle is uniquely structured to achieve very rapid divisions with little tolerance of DNA damage. This study investigates the specific requirement for Sin3a in the early mouse embryo and shows that embryos lacking Sin3a suffer unresolved DNA damage and acute p53-independent apoptosis specifically in the E3.5–4.5 epiblast. Surprisingly, Myc and E2F targets in Sin3a-null ICMs are downregulated, suggesting a central but non-canonical role for Sin3a in regulating the pluripotent embryonic cell cycle. ES cells deleted for Sin3a mount a DNA damage response indicative of unresolved double-strand breaks, profoundly arrest at G2, and undergo apoptosis. These results indicate that Sin3a protects the genomic integrity of pluripotent embryonic cells and governs their unusual cell cycle.
Highlights ► Sin3a is required for proliferation and survival of pluripotent embryonic cells. ► Sin3a-/- mouse ICM cells are eliminated by p53-independent apoptosis. ► Sin3a is a critical regulator of the unusual pluripotent embryonic cell cycle. ► Sin3a prevents or repairs DSBs that arise in ES cells, perhaps during replication. ► The Sin3a interactome provides insights into function Sin3a in ES cells.
Databáze: OpenAIRE
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