Mammary-specific gene activation is defined by progressive recruitment of STAT5 during pregnancy and the establishment of H3K4me3 marks
Open accessAbstract
Differentiation of mammary secretory epithelium during pregnancy is characterized by sequential activation of genes over several orders of magnitude. Although the transcription factor STAT5 is key to alveolar development, it is not clear to what extent it controls temporal activation of genetic programs in secretory epithelium. To uncover molecular mechanisms effecting progressive differentiation, we explored genome-wide STAT5 binding and H3K4me3 (i.e., trimethylated histone H3 at K4) marks in mammary tissues at early and midpregnancy and at parturition. STAT5 binding to genes induced during pregnancy was low in immature mammary tissue but increased with epithelial differentiation. Increased STAT5 binding was associated with the establishment of H3K4me3 marks and transcriptional activation. STAT5 binding preceded the formation of H3K4me3 marks in some mammary-specific genes. De novo STAT5 binding was also found at distal sites, indicating enhancers. Furthermore, we established an exhaustive mammary transcriptome. Through integration of RNA-seq and STAT5 and H3K4me4 ChIP-seq data, we discovered novel mammary-specific alternative promoters and genes, including noncoding RNAs. Our findings suggest that STAT5 is an early step in establishing transcription complexes on genes specifically expressed in mammary epithelium. This is the first study in an organ that links progressive chromatin occupancy of STAT5 to the acquisition of H3K4me3 marks and transcription during hormone-induced differentiation.
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In vivo studies show that PRL has a selective stimulatory effect on adrenal androgen production.
“These data are also consistent with the in vivo studies cited before showing that PRL has a selective stimulatory effect on adrenal androgen production 12,23-29 .”
From ACTH and prolactin synergistically and selectively regulate CYP17 expression and adrenal androgen production in human foetal adrenal organ cultures (2023) · cites this paper as [23]
A number of studies have described an association of hyperprolactinemia with increased adrenal androgen levels and an increased adrenocortical response to ACTH in patients with high circulating PRL levels.
“A number of studies have described the association of hyperprolactinemia with increased adrenal androgen levels and an increased adrenocortical response to ACTH in patients with high circulating PRL levels 12,23-29 .”
From ACTH and prolactin synergistically and selectively regulate CYP17 expression and adrenal androgen production in human foetal adrenal organ cultures (2023) · cites this paper as [23]
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581 · see citing works
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · see citing works
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · see citing works
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668 · see citing works
Warde-Farley, D., Donaldson, S. L., Comes, O., Zuberi, K., Badrawi, R., Chao, P., Franz, M., Grouios, C., Kazi, F., Lopes, C. T., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq537 · Cited by 4,835 · see citing works
A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells
Guenther, M. G., Levine, S. S., Boyer, L. A., Jaenisch, R., & Young, R. A. (2007) · Cell · doi:10.1016/j.cell.2007.05.042 · Cited by 1,946 · see citing works
MEME-ChIP: motif analysis of large DNA datasets
Machanick, P., & Bailey, T. L. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr189 · Cited by 1,815 · see citing works
A travel guide to Cytoscape plugins
Saito, R., Smoot, M. E., Ono, K., Ruscheinski, J., Wang, P., Lotia, S., Pico, A. R., Bader, G. D., & Ideker, T. (2012) · Nature Methods · doi:10.1038/nmeth.2212 · Cited by 1,496 · see citing works
A map of the cis-regulatory sequences in the mouse genome
Shen, Y., Yue, F., McCleary, D. F., Ye, Z., Edsall, L., Kuan, S., Wagner, U., Dixon, J., Lee, L., Lobanenkov, V. V., et al. (2012) · Nature · doi:10.1038/nature11243 · Cited by 1,361 · see citing works
Identification of novel transcripts in annotated genomes using RNA-Seq
Roberts, A., Pimentel, H., Trapnell, C., & Pachter, L. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr355 · Cited by 963 · see citing works
Cui, K., Zang, C., Roh, T., Schones, D. E., Childs, R. W., Peng, W., & Zhao, K. (2009) · Cell stem cell · doi:10.1016/j.stem.2008.11.011 · Cited by 620 · see citing works
Information networks in the mammary gland
Hennighausen, L. G., & Robinson, G. W. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1714 · Cited by 506 · see citing works
Hormone Action in the Mammary GlandPreprint
Brisken, C., & O’Malley, B. W. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003178 · Cited by 453 · see citing works
STATs Shape the Active Enhancer Landscape of T Cell Populations
Vahedi, G., Takahashi, H., Nakayamada, S., Sun, H., Sartorelli, V., Kanno, Y., & O’Shea, J. J. (2012) · Cell · doi:10.1016/j.cell.2012.09.044 · Cited by 365 · see citing works
The Ets transcription factor Elf5 specifies mammary alveolar cell fatePreprint
Oakes, S. R., Naylor, M. J., Asselin-Labat, M.-L., Blazek, K. D., Gardiner‐Garden, M., Hilton, H. N., Kazlauskas, M., Pritchard, M. A., Chodosh, L. A., Pfeffer, P., et al. (2008) · Genes & Development · doi:10.1101/gad.1614608 · Cited by 260 · see citing works
Robinson, G. W., Johnson, P. F., Hennighausen, L. G., & Sterneck, E. (1998) · Genes & Development · doi:10.1101/gad.12.12.1907 · Cited by 257 · see citing works
Seagroves, T. N., Krnacik, S., Raught, B., Gay, J. P., Burgess-Beusse, B. L., Darlington, G., & Rosen, J. M. (1998) · Genes & Development · doi:10.1101/gad.12.12.1917 · Cited by 253 · see citing works
Production of Human Tissue Plasminogen Activator in Transgenic Mouse Milk
Gordon, K., Lee, E., Vitale, J. A., Smith, A. E., Westphal, H., & Hennighausen, L. G. (1987) · Nature Biotechnology · doi:10.1038/nbt1187-1183 · Cited by 195 · see citing works
Mandal, M., Powers, S. E., Maienschein‐Cline, M., Bartom, E. T., Hamel, K. M., Kee, B. L., Dinner, A. R., & Clark, M. R. (2011) · Nature Immunology · doi:10.1038/ni.2136 · Cited by 187 · see citing works
Pittius, C. W., Hennighausen, L. G., Lee, E., Westphal, H., Nicols, E., Vitale, J. A., & Gordon, K. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.16.5874 · Cited by 178 · see citing works
Zhang, Y., Laz, E. V., & Waxman, D. J. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.06312-11 · Cited by 171 · see citing works
Shi, L., & Rosen, J. M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.4.2063 · Cited by 162 · see citing works
Zhou, J., Chehab, R., Tkalcevic, J., Naylor, M. J., Harris, J., Wilson, T. J., Tsao, S., Tellis, I., Zavarsek, S., Xu, D., et al. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600538 · Cited by 156 · see citing works
Sugathan, A., & Waxman, D. J. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00280-13 · Cited by 135 · see citing works
Burdon, T. G., Maitland, K., Clark, A., Wallace, R. M., & Watson, C. J. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.11.7877621 · Cited by 94 · see citing works
Yamaji, D., Kang, K., Robinson, G. W., & Hennighausen, L. G. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1310 · Cited by 82 · see citing works
Kabotyanski, E. B., Huetter, M., Xian, W., Rijnkels, M., & Rosen, J. M. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0160 · Cited by 79 · see citing works
Kang, K., Robinson, G., & Hennighausen, L. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-4 · Cited by 72 · see citing works
Kabotyanski, E. B., Rijnkels, M., Freeman-Zadrowski, C., Buser, A. C., Edwards, D. P., & Rosen, J. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.032490 · Cited by 65 · see citing works
The spectrum of STAT functions in mammary gland development
Hughes, K., & Watson, C. J. (2012) · JAK-STAT · doi:10.4161/jkst.19691 · Cited by 60 · see citing works
Deng, C., Li, Y., Liang, S. Y., Cui, K., Salz, T., Yang, H., Tang, Z., Gallagher, P. G., Qiu, Y., Roeder, R. G., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003524 · Cited by 60 · see citing works
LaMarca, H. L., Visbal, A. P., Creighton, C. J., Liu, H., Zhang, Y., Behbod, F., & Rosen, J. M. (2010) · Stem Cells · doi:10.1002/stem.297 · Cited by 57 · see citing works
Rijnkels, M., Freeman-Zadrowski, C., Hernandez, J., Potluri, V., Wang, L., Li, W., & Lemay, D. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053270 · Cited by 57 · see citing works
Generation of bivalent chromatin domains during cell fate decisions
Gobbi, M. D., Garrick, D., Lynch, M., Vernimmen, D., Hughes, J. R., Goardon, N., Luc, S., Lower, K. M., Sloane-Stanley, J. A., Pina, C., et al. (2011) · Epigenetics & Chromatin · doi:10.1186/1756-8935-4-9 · Cited by 57 · see citing works
Shore, A. N., Kabotyanski, E. B., Roarty, K. P., Smith, M. A., Zhang, Y., Creighton, C. J., Dinger, M. E., & Rosen, J. M. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002840 · Cited by 56 · see citing works
Dynamic regulation of epigenomic landscapes during hematopoiesis
Abraham, B. J., Cui, K., Tang, Q., & Zhao, K. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-193 · Cited by 55 · see citing works
McKnight, R. A., Spencer, M., Wall, R. J., & Hennighausen, L. G. (1996) · Molecular Reproduction and Development · doi:10.1002/(sici)1098-2795(199606)44:2 · Cited by 54 · see citing works
Lee, H. J., & Ormandy, C. J. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.02.006 · Cited by 38 · see citing works
Tarulli, G. A., Silva, D. D., Ho, V. C. Y., Kunasegaran, K., Ghosh, K., Tan, B. C., Bulavin, D. V., & Pietersen, A. M. (2013) · Breast Cancer Research · doi:10.1186/bcr3381 · Cited by 25 · see citing works
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Mechanisms and consequences of Jak–STAT signaling in the immune system
Villarino, A. V., Kanno, Y., & O'Shea, J. J. (2017) · Nature Immunology · doi:10.1038/ni.3691 · Cited by 1,221 · see citing works
The potential and controversy of targeting STAT family members in cancer
Verhoeven, Y., Tilborghs, S., Jacobs, J., De Waele, J., Quatannens, D., Deben, C., Prenen, H., Pauwels, P., Trinh, X. B., Wouters, A., et al. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.10.002 · Cited by 409 · see citing works
Hierarchy within the mammary STAT5-driven Wap super-enhancer
Shin, H. Y., Willi, M., Yoo, K. H., Zeng, X., Wang, C., Metser, G., & Hennighausen, L. (2016) · Nature Genetics · doi:10.1038/ng.3606 · Cited by 282 · see citing works
An Epigenetic Memory of Pregnancy in the Mouse Mammary Gland
dos Santos, C. O., Dolzhenko, E., Hodges, E. C., Smith, A. D., & Hannon, G. J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.015 · Cited by 145 · see citing works
Kim, T., Seo, H. D., Hennighausen, L. G., Lee, D., & Kang, K. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky083 · Cited by 71 · see citing works
HDAC6 Deacetylates HMGN2 to Regulate Stat5a Activity and Breast Cancer Growth
Medler, T. R., Craig, J. M., Fiorillo, A. A., Feeney, Y. B., Harrell, J. C., & Clevenger, C. V. (2016) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0109 · Cited by 52 · see citing works
An autoregulatory enhancer controls mammary-specific STAT5 functions
Metser, G., Shin, H. Y., Wang, C., Yoo, K. H., Oh, S., Villarino, A. V., O’Shea, J. J., Kang, K., & Hennighausen, L. G. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv999 · Cited by 45 · see citing works
Schauwecker, S. M., Kim, J. J., Licht, J. D., & Clevenger, C. V. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.764233 · Cited by 33 · see citing works
Vapola, M. H., Rokka, A., Sormunen, R. T., Alhonen, L. I., Schmitz, W., Conzelmann, E., Wärri, A. M., Grunau, S., Antonenkov, V. D., & Hiltunen, J. K. (2014) · Developmental Biology · doi:10.1016/j.ydbio.2014.03.022 · Cited by 28 · see citing works
Lee, H., Willi, M., Wang, C., Yang, C. M., Smith, H. E., Liu, C., & Hennighausen, L. G. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx185 · Cited by 25 · see citing works
Brady, N. J., Farrar, M. A., & Schwertfeger, K. L. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.06.007 · Cited by 24 · see citing works
Coregulation of genetic programs by the transcription factors NFIB and STAT5.
Robinson, G., Kang, K., Yoo, K., Tang, Y., Zhu, B., Yamaji, D., Colditz, V., Jang, S.-J., Gronostajski, R., & Hennighausen, L. (2014) · Molecular Endocrinology · doi:10.1210/me.2012-1387 · Cited by 22 · see citing works
Differential cytokine sensitivities of STAT5-dependent enhancers rely onStat5autoregulation
Willi, M., Yoo, K. H., Wang, C., Trajanoski, Z., & Hennighausen, L. G. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw844 · Cited by 22 · see citing works
Yoo, K. H., Kang, K., Feuermann, Y., Jang, S. J., Robinson, G. W., & Hennighausen, L. G. (2014) · Developmental Biology · doi:10.1016/j.ydbio.2014.09.012 · Cited by 21 · see citing works
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Alamri, A. M., Kang, K., Groeneveld, S., Wang, W., Zhong, X., Kallakury, B., Hennighausen, L. G., Liu, X., & Furth, P. A. (2016) · Endocrine Related Cancer · doi:10.1530/erc-16-0071 · Cited by 20 · see citing works
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Varco-Merth, B., & Rotwein, P. S. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00324.2014 · Cited by 17 · see citing works
Zeng, X., Willi, M., Shin, H. Y., Hennighausen, L. G., & Wang, C. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.11.079 · Cited by 16 · see citing works
Wu, A. M. L., Yang, M., Dalvi, P., Turinsky, A. L., Wang, W., Butcher, D. T., Egan, S. E., Weksberg, R., Harper, P. A., & Ito, S. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00323.2014 · Cited by 15 · see citing works
Casey, T., Suárez-Trujillo, A., Cummings, S., Huff, K., Crodian, J. S., Bhide, K. P., Aduwari, C., Teeple, K., Shamay, A., Mabjeesh, S. J., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248199 · Cited by 15 · see citing works
Lee, H., Willi, M., Kuhns, T. M., Liu, C., & Hennighausen, L. G. (2021) · Nature Communications · doi:10.1038/s41467-021-22500-w · Cited by 14 · see citing works
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Ortiz, J. R., Lewis, S. M., Ciccone, M. F., Chatterjee, D., Henry, S., Siepel, A. C., & dos Santos, C. O. (2024) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-023-09553-x · Cited by 13 · see citing works
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Assefnia, S., Kang, K., Groeneveld, S., Yamaji, D., Dabydeen, S. A., Alamri, A. M., Liu, X., Hennighausen, L. G., & Furth, P. A. (2014) · Endocrine Related Cancer · doi:10.1530/erc-14-0032 · Cited by 12 · see citing works
Hakim, S., Craig, J. M., Koblinski, J. E., & Clevenger, C. V. (2020) · iScience · doi:10.1016/j.isci.2020.101581 · Cited by 12 · see citing works
Zhang, H., Li, H. S., & Watowich, S. S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-374279-7.11015-x · Cited by 7 · see citing works
Lee, H., Jankowski, J., Liu, C., & Hennighausen, L. G. (2025) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-025-09582-8 · Cited by 4 · see citing works
Schneider, G., Ruggiero, C., Renault, L., Doghman-Bouguerra, M., Durand, N., Hingrai, G., Dijoud, F., Plotton, I., & Lalli, E. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad118 · Cited by 3 · see citing works
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Deravi, N., & Rezaei, N. (2023) · Interdisciplinary cancer research · doi:10.1007/16833_2022_107 · Cited by 3 · see citing works
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An automated analysis pipeline for a large set of ChIP-seq data: AutoChIP
Kim, T., Lee, W., Han, K., & Kang, K. (2014) · Genes & Genomics · doi:10.1007/s13258-014-0260-3 · Cited by 2 · see citing works
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Zhang, H., Li, H. S., & Watowich, S. S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-128-24465-4.00508-1
- Authors
- Kang, K., Yamaji, D., Yoo, K. H., Robinson, G. W., & Hennighausen, L.
- Affiliations
- National Institutes of Health (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2014-02-01
- Volume
- 34
- Issue
- 3
- Pages
- 464-473
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3911501
- OpenAlex
- W1987606503
- Cited by
- 35
- References
- 41
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 8 · 2015: 3 · 2014: 8
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Economía y Competitividad
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- STAT5, H3K4me3, mammary gland development, pregnancy, alveolar differentiation, enhancers, alternative promoters, non-coding RNA, chromatin occupancy, transcriptional activation, childbirth
- MeSH terms
- Animals, Animals, Newborn, Chromatin, Epithelium, Female, Histones, Lysine, Mammary Glands, Animal, Methylation, Phosphorylation, Pregnancy, Promoter Regions, Genetic, Protein Binding, Transcriptional Activation, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, STAT5 Transcription Factor, Mice, Transcriptome, Gene Ontology
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