These authors contribute equally to the present study.
Menstrual cycle-dependent febrile episode mediated by sequence-specific repression of poly(ADP-ribose) polymerase-1 on the transcription of the human serotonin receptor 1A gene†
Article first published online: 7 NOV 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 1, pages 209–217, January 2012
How to Cite
Jiang, Y.-C., Wu, H.-M., Cheng, K.-H. and Sunny Sun, H. (2012), Menstrual cycle-dependent febrile episode mediated by sequence-specific repression of poly(ADP-ribose) polymerase-1 on the transcription of the human serotonin receptor 1A gene. Hum. Mutat., 33: 209–217. doi: 10.1002/humu.21622
Communicated by Daniel W. Norburt
- Issue published online: 14 DEC 2011
- Article first published online: 7 NOV 2011
- Accepted manuscript online: 11 OCT 2011 01:36PM EST
- Manuscript Accepted: 16 SEP 2011
- Manuscript Received: 30 JUN 2011
- National Science Council, Taiwan. Grant Number: 99-3112-B-006-002
- transcriptional repressor;
The serotonin receptor 1A (encoded by the HTR1A gene) plays a critical role in serotonergic transmission and was linked with many human diseases. A 33-year-old woman with rare menstrual cycle-dependent fever showed abnormal estrogen profile and responded well to the HTR1A agonist buspirone, suggesting that her fevers were allied to estrogen-related HTR1A deficiency. We identified an adenine deletion 480-bases upstream of the translation start site (i.e., -480delA) of HTR1A in this patient. To determine the underlying mechanism of -480delA-mediated HTR1A deficiency, we first showed that HTR1A -480 region can be bound by multiple nuclear protein(s). We then identified poly(ADP-ribose) polymerase (PARP1) as one of the proteins that binds to HTR1A -480 region. Using PARP1 overexpression and knockdown, our data demonstrated that PARP1 represses HTR1A transcription. Furthermore, HTR1A -480delA promoter possesses increased interaction with PARP1 and caused an additional reduction in transcription. Finally, 17β-estradiol administration further reduced transcription associated with the mutant promoter. Altogether, these data suggest that estrogen-induced hyperactivity of HTR1A mutant promoter causes the reduction of HTR1A mRNA and leads to the disruption of HTR1A-mediate hypothermic regulation. This is the first report of HTR1A mutation underlying menstrual cycle-dependent febrile episodes, and implies that similar “febrile episode” cases may also result from the dysfunction of serotonin transmission. Hum Mutat 33:209–217, 2012. © 2011 Wiley Periodicals, Inc.