title: Positive regulation of additional sex comb-like 1 gene expression by the pluripotency factor SOX2.
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 -1400 bp. 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.
authors.affiliation: Department of Bioscience & Biotechnology, Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Myengmo
authors.initials: M
authors.lastname: Kang
authors.forename: Sang-Wang
authors.initials: SW
authors.lastname: Lee
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Um
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C473949:ASXL1 protein, human; D012097:Repressor Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors