While the complex mechanisms timing human birth remain elusive, a major role has been proposed for the placenta. A number of studies support existence of a placental clock that determines length of human pregnancy. Recently we have determined that an epigenetic switch is ultimately responsible for positive regulation of corticotropin-releasing hormone (CRH), part of the placental clock, by glucocorticoids as gestation advances
At present, we are employing epigenetic, genomic, proteomic, and biochemical approaches in both in vitro (primary trophoblast and human embryonic stem cells) and in vivo (non-human primate) models, to understand the molecular regulation and functions of “pro-labor” genes as well as the pathway(s) leading to functional withdrawal of progesterone in the context of initiation of human labor at term.
DiStefano V, Wang B*. Parobchak N, Roche N, Rosen T* (2015). RelB/p52-associated CBP/HDAC1 mediate acetylation/de-acetylation of H3K9 to upregulate CRH in term human placenta. Sci Signal (In press) (Selected for Podcast).
Rosen T*, Schulkin J, Power M, Tadesse S, Norwitz ER, and Wang B* (2015). Comparative immunohistochemistry of placental CRH and RelB/NF-κB2 between human and non-human primates. Comparative Med. 65:140-143.
Yu LJ, Wang B*, Parobchak N, Roche N, Rosen T* (2015). STAT3 cooperates with the non-canonical NF-κB signaling to regulate pro-labor genes in the human placenta. Placenta. 36:581-586.
Wang B*, Parobchak N, Rosen M, Roche, N, and Rosen T* (2014). Negative effects of progesterone receptor isoform-A on human placental activity of the non-canonical NF-κB signaling. J Clin Endocrinol Metab. 99:E320-328.
Wang B*, Palomares K, Parobchak N, Cece J, Rosen M, Nguyen A, Rosen T* (2013). Glucocorticoid receptor signaling contributes to constitutive activation of the noncanonica NF-κB pathway in term human placenta. Mol Endocrinol 27:203-211 (Featured in Endocrine News, April, 2013).
Wang B*, Parobchak N, and Rosen T* (2012). RelB/NF-κB2 regulates corticotropin-releasing hormone in the human placenta (2012). Mol Endocrinol 26:1356-1369 (Featured in Endocrine News, August, 2012).
1. ConSite for identifying cis-regulatory elements in genomic sequences (http://consite.genereg.net/).
2. Transcriptional Regulatory Element Database (https://cb.utdallas.edu/cgi-bin/TRED/tred.cgi?process=home).
3. GenePattern for analysis of gene expression (http://www.broadinstitute.org/cancer/software/genepattern/).
4. KEGG for understanding high-level functions and utilities of the biological system (http://www.genome.jp/kegg/).
5. DAVID for functional annotation of genes (https://david.ncifcrf.gov/).
6. NIH Roadmap Epigenomics Mapping Consortium (http://www.roadmapepigenomics.org/)