Lena Kabotyanski, Ph.D.
One of the major goals of our laboratory is to understand the mechanisms by which hormones and growth factors regulate normal mammary gland development and how these same signaling pathways become altered in breast cancer. Specific interest has been placed upon studying the mechanisms by which the lactogenic hormones, prolactin and glucocorticoids, regulate milk protein gene expression.
In our study we focused on mechanism of hormonal regulation of ß-casein gene expression in normal mammary epithelial cells. Using ChIP assays, we determined the dynamics of recruitment/occupancy of transcription factors Stat5, GR, C/EBPß and YY-1 at the hormonally activated ß-casein proximal promoter and distal enhancer which is 6 kb upstream of the transcription start site. In addition, we investigated the recruitment of p300, which is involved in ß-casein expression and possesses post-translational modification activity. We also studied the dynamics of histone acetylation and established the time course of RNA Pol II and phosphorylated RNA Pol II accumulation at both regulatory regions of the hormonally activated ß-casein gene. Using a chromosome conformation capture (3C) assay and quantitative real-time PCR, we have demonstrated that the hormonally activated ß-casein proximal promoter and distal enhancer communicate with each other through the direct physical interactions forming a chromatin loop. The communication between these regulatory regions with intervening DNA looping is a critical step required to both create and maintain active chromatin domains and regulate transcription.
- Joined Lab: October 1996
- Position: Research Associate
- Degrees: BA, Altay State University (Russia), 1982
Ph.D., Institute of Organic Chemistry, Russian Academy of Sciences, 1986
Rijnkels M, Kabotyanski E, Montazer-Torbati MB, Beauvais CH, Vassetzky Y, Rosen JM, Devinoy E. The epigenetic landscape of mammary gland development and functional differentiation. J Mammary Gland Biol Neoplasia 2010; 15(1): 85-100
Kabotyanski EB, Rijnkels M, Freeman-Zadrowski C, Buser AC, Edwards DP, Rosen JM. Lactogenic hormonal induction of long distance interactions between beta-casein gene regulatory elements. J Biol Chem. 2009; 284(34): 22815-24
Kabotyanski EB, Rijnkels M, Buser AC, Edwards DP, Rosen JM. Lactogenic hormonal induction of long distance interactions between ß-casein gene regulatory elements J. Biol. Chem. 2009 Jun 19. [Epub ahead of print]
Kabotyanski EB, Hutter M, Xian W, Rijnkels M, and Rosen JM. Integration of prolactin and glucocorticoid signaling at the ß-casein promoter and enhancer by ordered recruitment of specific transcription factors and chromatin modifiers. Mol Endo. 2006; 20(10):2355–2368.
Kabotyanski EB, Rosen JM. Signal transduction pathways regulated by prolactin and Src result in different conformations of activated Stat5b. J Biol Chem. 2003 May 9;278(19):17218-27.
Grimm SL, Seagroves TN, Kabotyanski EB, Hovey RC, Vonderhaar BK, Lydon JP, Miyoshi K, Hennighausen L, Ormandy CJ, Lee AV, Stull MA, Wood TL, Rosen JM. Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development. Mol Endocrinol. 2002 Dec;16(12):2675-91.
Kazansky AV, Kabotyanski EB, Wyszomierski SL, Mancini MA, Rosen JM. Differential effects of prolactin and src/abl kinases on the nuclear translocation of STAT5B and STAT5A. J Biol Chem. 1999 Aug 6;274(32):22484-92.
Kabotyanski EB, Gomelsky L, Han JO, Stamato TD, Roth DB. Double-strand break repair in Ku86- and XRCC4-deficient cells. Nucleic Acids Res. 1998 Dec 1;26(23):5333-42.
Kabotyanski EB, Zhu C, Kallick DA, Roth DB. Hairpin opening by single-strand-specific nucleases. Nucleic Acids Res. 1995 Oct 11;23(19):3872-81.