[Abstract Title]. - Society for Neuroscience

Authors: *B. WU 1 , K. CHEN 1 , Y. LI 3 , Y.-F. C. LAU 3 , J. C. SHIH 2 ;
1 Pharmacol & Pharm. Sci., 2 Pharmacol & Pharm. Sci., Cell & Neurobio., Univ. Southern Calif,
Los Angeles, CA; 3 Dept. of Med., Univ. of California, San Francisco, San Francisco, CA
Abstract: The transcriptional regulation of monoamine oxidase (MAO) A has been extensively
studied in this laboratory. Sp1 activates MAO A core promoter via several Sp1-binding sites.
Two novel transcription factors R1 (RAM2/CDCA7L/JPO2) and EAPP compete with Sp1 and
repress MAO A promoter by binding to Sp1-binding sites. This is the first study showing that
SRY (sex-determining region on the Y chromosome) interacts with Sp1 and activates MAO A
promoter activity in human male neuroblastoma BE(2)C cells.
The SRY gene, encoding a putative transcription factor, plays a key role in testis determination
and differentiation during embryogenesis. Although many pathways regulating sexual
developmental process have been elucidated, direct downstream targets of SRY are still unclear.
MAO A has been recently identified as a potential target by ChIP-chip assay.
Transient co-transfection and luciferase assay showed that human SRY but not mouse Sry
significantly increased human MAO A promoter activity in BE(2)C and human prostate
carcinoma C42B cell lines by 3-7 folds and 8-15 folds, respectively. This activation was SRY
concentration-dependent. siRNA-mediated endogenous SRY knockdown reduced MAO A
promoter activity by 60% in BE(2)C cells. Moreover, serial deletion analysis of the MAO A
promoter revealed that putative SRY-binding sites were located in the 0.2 kb core promoter
region, which contained several Sp1-binding sites as shown previously. Co-transfection of
various amounts of Sp1 enhanced SRY activation of MAO A promoter in a Sp1-concentration
dependent manner, indicating that Sp1 interacted with SRY in MAO A promoter. The MAO A
promoter activity reduced significantly by 50% after Sp1 was knocked down by siRNA,
however, the fold of the increase of the SRY activation of MAO A promoter activity remained
the same, suggesting that SRY may interact with other transcription factors in addition to Sp1.
Taken together, this study has demonstrated that the interaction of SRY with Sp1 and other
transcription factors activated MAO A promoter activity. Considering the important
physiological role of SRY, this study provides new insights into the novel function of MAO A in
SRY-associated developmental processes.
Disclosures: B. Wu , None; K. Chen, None; Y. Li, None; Y.C. Lau, None; J.C. Shih, None.
Poster
278. Sex Differences I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 278.8/MM1
Topic: E.01.e. Sexual differences