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An acetylation-enhanced interaction between transcription factor Sox2 and the steroid receptor coactivators facilitates Sox2 transcriptional activity and function
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2021
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2021.
-
Abstract
- Sox2 (SRY-box 2) is a transcription factor with critical roles in maintaining embryonic and adult stem cell functions and in tumorigenesis. However, how Sox2 exerts its transcriptional function remains unclear. Here we used an in vitro protein-protein interaction assay to discover transcriptional regulators for embryonic stem cell core transcription factors (Oct4, Sox2, Klf4 and c-Myc) and identified members of the steroid receptor coactivators (SRCs) as Sox2-specific interacting proteins. The SRC family coactivators have broad roles in transcriptional regulation, but it is unknown whether they also serve as Sox2 coactivators. We demonstrated that these proteins facilitate Sox2 transcriptional activity and acts synergistically with p300. Furthermore, we uncovered an acetylation-enhanced interaction between Sox2 and SRC-2/3, but not SRC-1, demonstrating it is Sox2 acetylation that promotes the interaction. We identified putative Sox2 acetylation sites required for acetylation-enhanced interaction between Sox2 and SRC-3, and demonstrated that acetylation on these sites contributes to Sox2 transcriptional activity and recruitment of SRC-3. We showed that activation domains 1 (AD1) and 2 (AD2) of SRC-3 both display a preferential binding to acetylated Sox2. Finally, functional analyses in mouse embryonic stem (ES) cells demonstrated that knockdown of SRC-2/3 but not SRC-1 in mouse ES cells significantly down-regulates the transcriptional activities of various Sox2 target genes and impairs ES cell stemness. Taken together, we identify specific SRC family proteins as novel Sox2 coactivators and uncover the role of Sox2 acetylation in promoting coactivator recruitment and Sox2 transcriptional function.
- Subjects :
- Sox2, SRY-box 2
Transcription, Genetic
NCOAs, nuclear receptor coactivators
Biochemistry
Nuclear Receptor Coactivator 3
Mice
Nuclear Receptor Coactivator 2
Nuclear Receptor Coactivator 1
Transcription (biology)
Transcriptional regulation
TSA, trichostatin A
SRC-1
AD2, activation domain 2
co-IP, co-immunoprecipitation
SRC-2
SRC-3
Acetylation
Cell biology
ChIP, chromatin immunoprecipitation
WB, Western blot
KLF4
embryonic structures
biological phenomena, cell phenomena, and immunity
transcription
Adult stem cell
Research Article
p300
Biology
steroid receptor coactivators
NAM, nicotinamide
SOX2
stomatognathic system
Coactivator
Animals
Humans
Molecular Biology
Transcription factor
NaCro, sodium crotonate
SOXB1 Transcription Factors
fungi
ES, embryonic stem
Cell Biology
pluripotency
SRCs, steroid receptor coactivators
HEK293 Cells
NRs, nuclear hormone receptors
Sox2 acetylation
sense organs
AD1, activation domain 1
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 1083351X and 00219258
- Volume :
- 297
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- The Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....3fc871e08c423a1d049bce37de141753