RevSex duplication-induced and sex-related differences in the SOX9 regulatory region chromatin landscape in human fibroblasts

Lybaek, Helle, de Bruijn, Diederik, den Engelsman-van Dijk, Anke H. A., Vanichkina, Darya, Nepal, Chirag, Brendehaug, Atle and Houge, Gunnar (2014) RevSex duplication-induced and sex-related differences in the SOX9 regulatory region chromatin landscape in human fibroblasts. Epigenetics, 9 3: 416-427. doi:10.4161/epi.27474


Author Lybaek, Helle
de Bruijn, Diederik
den Engelsman-van Dijk, Anke H. A.
Vanichkina, Darya
Nepal, Chirag
Brendehaug, Atle
Houge, Gunnar
Title RevSex duplication-induced and sex-related differences in the SOX9 regulatory region chromatin landscape in human fibroblasts
Formatted title
RevSex duplication-induced and sex-related differences in the SOX9 regulatory region chromatin landscape in human fibroblasts
Journal name Epigenetics   Check publisher's open access policy
ISSN 1559-2294
1559-2308
Publication date 2014-03-01
Year available 2013
Sub-type Article (original research)
DOI 10.4161/epi.27474
Open Access Status DOI
Volume 9
Issue 3
Start page 416
End page 427
Total pages 12
Place of publication Austin, TX, United States
Publisher Landes Bioscience
Language eng
Formatted abstract
It was recently shown that duplications of the RevSex element, located 0.5 Mb upstream of SOX9, cause XX-disorder of sex development (DSD), and that deletions cause XY-DSD. To explore how a 148 kb RevSex duplication could have turned on gonadal SOX9 expression in the absence of SRY in an XX-male, we examined the chromatin landscape in primary skin fibroblast cultures from the index, his RevSex duplication-carrier father and six controls. The ENCODE project supports the notion that chromatin state maps show overlap between different cell types, i.e., that our study of fibroblasts could be of biological relevance. We examined the SOX9 regulatory region by high-resolution ChIP-on-chip experiments (a kind of “chromatin-CGH”) and DNA methylation investigations. The RevSex duplication was associated with chromatin changes predicting better accessibility of the SRY-responsive TESCO enhancer region 14–15 kb upstream of SOX9. Four kb downstream of the TESCO evolutionary conserved region, a peak of the enhancer/promoter-associated H3K4me3 mark was found together with a major dip of the repressive H3K9me3 chromatin mark. Similar differences were also found when three control males were compared with three control females. A marked male/female difference was a more open chromatin signature in males starting ~400 kb upstream of SOX9 and increasing toward the SOX9 promoter. In the RevSex duplication-carrier father, two positions of DNA hypomethylation were also found, one corresponding to the H3K4me3 peak mentioned above. Our results suggest that the RevSex duplication could operate by inducing long-range epigenetic changes. Furthermore, the differences in chromatin state maps between males and females suggest that the Y chromosome or X chromosome dosage may affect chromatin conformation, i.e., that sex-dependent gene regulation may take place by chromatin modification.
Keyword SOX9
Epigenetics
Chromatin
Sex determination
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 18 December 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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