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Positive regulation of additional sex comb-like 1 gene expression by the pluripotency factor SOX2

Positive regulation of additional sex comb-like 1 gene expression by the pluripotency factor SOX2

Authors :
Kang, Myengmo
Lee, Sang-Wang
Kim, Eun-Joo
Um, Soo-Jong
Source :
Biochemical & Biophysical Research Communications. May2012, Vol. 421 Issue 3, p621-626. 6p.
Publication Year :
2012

Abstract

Abstract: Additional sex comb-like 1 (ASXL1) has been suggested to be an enhancer of trithorax and polycomb proteins, and functions as a dual co-regulator of retinoid acid (RA) signaling. However, the mechanism by which ASXL1 gene expression is regulated remains unresolved. Concomitant downregulation of both SOX2 and ASXL1 during the RA-induced differentiation of P19 cells prompted us to investigate the role of SOX2 in the regulation of ASXL1. Knockdown of SOX2 in SOX2-rich NT2 cells resulted in the reduction of ASXL1 expression, whereas SOX2 overexpression in SOX2-deficient H1299 cells increased ASXL1 expression. Using a cloned ASXL1–luciferase reporter, we demonstrated that SOX2 directly transactivates the ASXL1 promoter. Serial deletion and mutation studies mapped the SOX2 response element region in the ASXL1 promoter to −1600 to −1400bp. We showed by chromatin immunoprecipitation assay that SOX2 directly binds to the ASXL1 promoter region. Finally, formation of embryonic bodies by ASXL1-depleted murine E14TG2a embryonic stem cells was significantly impaired, similar to SOX2-knockdown cells. From these results, we suggest that ASXL1 may be a direct target of SOX2 and may play a role in maintaining the pluripotency of stem cells. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
0006291X
Volume :
421
Issue :
3
Database :
Academic Search Index
Journal :
Biochemical & Biophysical Research Communications
Publication Type :
Academic Journal
Accession number :
75165138
Full Text :
https://doi.org/10.1016/j.bbrc.2012.04.072