Myles Brown

Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers (2009)

Eeckhoute, Jérôme, Lupien, Mathieu, Meyer, Clifford A., Verzi, Michael P., Shivdasani, Ramesh A., Liu, X. Shirley, ...

Selective activity of a specific set of enhancers defines tissue-specific gene transcription. The pioneer factor FOXA1 has been shown to induce functional enhancer competency through chromatin...

Estradiol-regulated microRNAs control estradiol response in breast cancer cells (2009)

Bhat-Nakshatri, Poornima, Wang, Guohua, Collins, Nikail R., Thomson, Michael J., Geistlinger, Tim R., Carroll, Jason S., ...

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). E2-inducible proteins c-Myc and...

Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery (2009)

Boros, Joanna, Donaldson, Ian J., O'Donnell, Amanda, Odrowaz, Zaneta A., Zeef, Leo, Lupien, Mathieu, ...

Transcription factors play an important role in orchestrating the activation of specific networks of genes through targeting their proximal promoter and distal enhancer regions. However, it is...

Model-based Analysis of ChIP-Seq (MACS) (2008)

Zhang, Yong, Liu, Tao, Meyer, Clifford A, Eeckhoute, Jérôme, Johnson, David S, Bernstein, Bradley E, ...

Abstract We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size of...

xMAN: extreme MApping of OligoNucleotides (2008)

Li, Wei, Carroll, Jason S, Brown, Myles, Liu, X Shirley

Abstract Background The ability to rapidly map millions of oligonucleotide fragments to a reference genome is crucial to many high throughput genomic technologies. Results We propose an intuitive and...

Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets. (2008)

Johnson, David S., Li, Wei, Gordon, D. Benjamin, Bhattacharjee, Arindam, Curry, Bo, Ghosh, Jayati, ...

The most widely used method for detecting genome-wide protein-DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first...

Estrogen-Dependent Signaling in a Molecularly Distinct Subclass of Aggressive Prostate Cancer (2008)

Setlur, Sunita R., Mertz, Kirsten D., Hoshida, Yujin, Demichelis, Francesca, Lupien, Mathieu, Perner, Sven, ...

Background The majority of prostate cancers harbor gene fusions of the 5′-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast...

Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets (2008)

Johnson, David S., Li, Wei, Gordon, D. Benjamin, Bhattacharjee, Arindam, Curry, Bo, Ghosh, Jayati, ...

The most widely used method for detecting genome-wide protein–DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first...

The OXR domain defines a conserved family of eukaryotic oxidation resistance proteins (2007)

Durand, Mathieu, Kolpak, Adrianne, Farrell, Timothy, Elliott, Nathan A, Shao, Wenlin, Brown, Myles, ...

Abstract Background The NCOA7 gene product is an estrogen receptor associated protein that is highly similar to the human OXR1 gene product, which functions in oxidation resistance. OXR genes are...

The OXR domain defines a conserved family of eukaryotic oxidation resistance proteins (2007)

Durand, Mathieu, Kolpak, Adrianne, Farrell, Timothy, Elliott, Nathan A, Shao, Wenlin, Brown, Myles, ...

Abstract Background The NCOA7 gene product is an estrogen receptor associated protein that is highly similar to the human OXR1 gene product, which functions in oxidation resistance. OXR genes are...

Primate-specific evolution of an LDLR enhancer (2006)

Wang, Qian-fei, Prabhakar, Shyam, Wang, Qianben, Moses, Alan M, Chanan, Sumita, Brown, Myles, ...

Background Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. Results In this...

Primate-Specific Evolution of an LDLR Enhancer (2006)

Wang, Qian-fei, Prabhakar, Shyam, Wang, Qianben, Moses, Alan M., Chanan, Sumita, Brown, Myles, ...

Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study, we...

A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer (2006)

Eeckhoute, Jérôme, Carroll, Jason S., Geistlinger, Timothy R., Torres-Arzayus, Maria I., Brown, Myles

Estrogen stimulates the proliferation of the most common type of human breast cancer that expresses estrogen receptor α (ERα) through the activation of the cyclin D1 (CCND1) oncogene. However, our...

The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers (2006)

Colilla, Susan, Kantoff, Philip W., Neuhausen, Susan L., Godwin, Andrew K., Daly, Mary B., Narod, Steven A., ...

Women with BRCA1 mutations are at an elevated risk for breast cancer. AIB1 (NCOA3/SRC3) genotype and smoking may alter this risk. We examined the differences in breast cancer risk by AIB1...

The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers (2005)

Colilla, Susan, Kantoff, Philip W., Neuhausen, Susan L., Godwin, Andrew K., Daly, Mary B., Narod, Steven A., ...

Women with BRCA1 mutations are at an elevated risk for breast cancer. AIB1 (NCOA3/SRC3) genotype and smoking may alter this risk. We examined the differences in breast cancer risk by AIB1...

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy (2003)

Shao, Wenlin, Brown, Myles

Abstract Estrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for...

Polymorphic repeat in AIB1 does not alter breast cancer risk (2000)

Christopher A, Haiman, Hankinson, Susan E, Spiegelman, Donna, Colditz, Graham A, Willett, Walter C, Speizer, Frank E, ...

Statement of findings We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses'...

Estrogen Receptor-Mediated Transcription In Vitro (1998)

Liu, Hong, Brown, Myles

Estrogen receptor (ER) is a ligand activated transcription activator. The detailed mechanism of ER mediated transcription is unclear. We demonstrated that ER mediated transcription in cell free...

Differential Regulation of Cell Cycle Progression in Human Breast Cancer Cell Lines by the Estrogen Receptor (1998)

Direnzo, James, Brown, Myles

Critical predictions as to the biological behavior, and thus the appropriate therapeutic strategy, of breast cancers can be made based upon the status of the estrogen receptor (ER). In support of DOD...

Differential Regulation of Cell Cycle Progression in Human Breast Cancer Cell Lines by the Estrogen Receptor (1998)

Direnzo, James, Brown, Myles

The goal of DOD grant # DAMD17-97-1-7069 is to understand the mechanisms by which ER mediates gene regulation and cell cycle progression. Estrogen-bound ER undergoes structural changes which favor...

The control of SV40 transcription during a lytic infection: late RNA synthesis in the presence of inhibitors of DNA replication (1977)

Rosenthal, Leonard J., Brown, Myles

The transition from early to late transcription of SV40 DNA in productively infected BSC-1 cells was analyzed using both inhibitors of DNA replication, and early (Group A) temperature sensitive (ts)...

Polymorphic repeat in AIB1 does not alter breast cancer risk

Haiman, Christopher A, Hankinson, Susan E, Spiegelman, Donna, Colditz, Graham A, Willett, Walter C, Speizer, Frank E, ...

We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We...

Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium

Shim, Woo-Shin, DiRenzo, James, DeCaprio, James A., Santen, Richard J., Brown, Myles, Jeng, Meei-Huey

Steroid receptor coactivator-1 (SRC-1) family members interact with steroid receptors, including estrogen receptor α (ERα) and progesterone receptor (PR), to enhance ligand-dependent transcription....

Specific association of estrogen receptor β with the cell cycle spindle assembly checkpoint protein, MAD2

Poelzl, Gerhard, Kasai, Yasuyo, Mochizuki, Naoki, Shaul, Philip W., Brown, Myles, Mendelsohn, Michael E.

Estrogen receptors (ERs) are ligand-activated transcription factors that regulate gene expression and cell growth. Two ERs now have been identified: ERα and the more recently discovered ERβ. The...

The CAG repeat within the androgen receptor gene and its relationship to prostate cancer

Giovannucci, Edward, Stampfer, Meir J., Krithivas, Krishna, Brown, Myles, Brufsky, Adam, Talcott, James, ...

The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic...

AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor

Font De Mora, Jaime, Brown, Myles

Growth factor modulation of estrogen receptor (ER) activity plays an important role in both normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are known to stimulate the...

BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

DiRenzo, James, Shang, Yongfeng, Phelan, Michael, Sif, Säid, Myers, Molly, Kingston, Robert, ...

Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1...

ERAP140, a Conserved Tissue-Specific Nuclear Receptor Coactivator

Shao, Wenlin, Halachmi, Shlomit, Brown, Myles

We report here the identification and characterization of a novel nuclear receptor coactivator, ERAP140. ERAP140 was isolated in a screen for ERα-interacting proteins using the ERα ligand binding...

Agonist and Chemopreventative Ligands Induce Differential Transcriptional Cofactor Recruitment by Aryl Hydrocarbon Receptor

Hestermann, Eli V., Brown, Myles

Aryl hydrocarbon receptor (AHR) is a transcription factor whose activity is regulated by environmental agents, including several carcinogenic agonists. We measured recruitment of AHR and associated...

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy

Shao, Wenlin, Brown, Myles

Estrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response...

Immunologic selection against simian virus-40 transformed cells: Concomitant loss of viral antigens and early viral gene sequences

Kuster, Jürgen M., Mora, Peter T., Brown, Myles, Khoury, George

A clonal line of highly oncogenic “spontaneously transformed” mouse cells (T AL/N clone 3) was transformed in tissue culture by simian virus 40 (SV40) and subsequently recloned. The clone of...

Coactivator AIB1 links estrogen receptor transcriptional activity and stability

Shao, Wenlin, Keeton, Erika Krasnickas, McDonnell, Donald P., Brown, Myles

Agonist-mediated degradation of estrogen receptor α (ERα) has been associated with its transcriptional activity. However, the mechanism by which ERα is targeted for degradation and whether there...

Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein

Yahata, Tetsuro, Shao, Wenlin, Endoh, Hideaki, Hur, Jingyung, Coser, Kathryn R., Sun, Huiping, ...

CITED1, a CBP/p300-binding nuclear protein that does not bind directly to DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for...

Polymorphic repeat in AIB1 does not alter breast cancer risk

Haiman, Christopher A, Hankinson, Susan E, Spiegelman, Donna, Colditz, Graham A, Willett, Walter C, Speizer, Frank E, ...

We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We...

Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium

Shim, Woo-Shin, DiRenzo, James, DeCaprio, James A., Santen, Richard J., Brown, Myles, Jeng, Meei-Huey

Steroid receptor coactivator-1 (SRC-1) family members interact with steroid receptors, including estrogen receptor α (ERα) and progesterone receptor (PR), to enhance ligand-dependent transcription....

Specific association of estrogen receptor β with the cell cycle spindle assembly checkpoint protein, MAD2

Poelzl, Gerhard, Kasai, Yasuyo, Mochizuki, Naoki, Shaul, Philip W., Brown, Myles, Mendelsohn, Michael E.

Estrogen receptors (ERs) are ligand-activated transcription factors that regulate gene expression and cell growth. Two ERs now have been identified: ERα and the more recently discovered ERβ. The...

The CAG repeat within the androgen receptor gene and its relationship to prostate cancer

Giovannucci, Edward, Stampfer, Meir J., Krithivas, Krishna, Brown, Myles, Brufsky, Adam, Talcott, James, ...

The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic...

AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor

Font De Mora, Jaime, Brown, Myles

Growth factor modulation of estrogen receptor (ER) activity plays an important role in both normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are known to stimulate the...

BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

DiRenzo, James, Shang, Yongfeng, Phelan, Michael, Sif, Säid, Myers, Molly, Kingston, Robert, ...

Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1...

ERAP140, a Conserved Tissue-Specific Nuclear Receptor Coactivator

Shao, Wenlin, Halachmi, Shlomit, Brown, Myles

We report here the identification and characterization of a novel nuclear receptor coactivator, ERAP140. ERAP140 was isolated in a screen for ERα-interacting proteins using the ERα ligand binding...

Agonist and Chemopreventative Ligands Induce Differential Transcriptional Cofactor Recruitment by Aryl Hydrocarbon Receptor

Hestermann, Eli V., Brown, Myles

Aryl hydrocarbon receptor (AHR) is a transcription factor whose activity is regulated by environmental agents, including several carcinogenic agonists. We measured recruitment of AHR and associated...

Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein

Yahata, Tetsuro, Shao, Wenlin, Endoh, Hideaki, Hur, Jingyung, Coser, Kathryn R., Sun, Huiping, ...

CITED1, a CBP/p300-binding nuclear protein that does not bind directly to DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for...

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy

Shao, Wenlin, Brown, Myles

Estrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response...

Immunologic selection against simian virus-40 transformed cells: Concomitant loss of viral antigens and early viral gene sequences

Kuster, Jürgen M., Mora, Peter T., Brown, Myles, Khoury, George

A clonal line of highly oncogenic “spontaneously transformed” mouse cells (T AL/N clone 3) was transformed in tissue culture by simian virus 40 (SV40) and subsequently recloned. The clone of...

Coactivator AIB1 links estrogen receptor transcriptional activity and stability

Shao, Wenlin, Keeton, Erika Krasnickas, McDonnell, Donald P., Brown, Myles

Agonist-mediated degradation of estrogen receptor α (ERα) has been associated with its transcriptional activity. However, the mechanism by which ERα is targeted for degradation and whether there...

Primate-specific evolution of an LDLR enhancer

Wang, Qian-fei, Prabhakar, Shyam, Wang, Qianben, Moses, Alan M, Chanan, Sumita, Brown, Myles, ...

Analysis of primate-specific evolution of the LDL receptor enhancer demonstrates a molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions.

Model-based analysis of tiling-arrays for ChIP-chip

Johnson, W. Evan, Li, Wei, Meyer, Clifford A., Gottardo, Raphael, Carroll, Jason S., Brown, Myles, ...

We propose a fast and powerful analysis algorithm, titled Model-based Analysis of Tiling-arrays (MAT), to reliably detect regions enriched by transcription factor chromatin immunoprecipitation (ChIP)...

A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer

Eeckhoute, Jérôme, Carroll, Jason S., Geistlinger, Timothy R., Torres-Arzayus, Maria I., Brown, Myles

Estrogen stimulates the proliferation of the most common type of human breast cancer that expresses estrogen receptor α (ERα) through the activation of the cyclin D1 (CCND1) oncogene. However, our...

Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets

Johnson, David S., Li, Wei, Gordon, D. Benjamin, Bhattacharjee, Arindam, Curry, Bo, Ghosh, Jayati, ...

The most widely used method for detecting genome-wide protein–DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first...

Model-based Analysis of ChIP-Seq (MACS)

Zhang, Yong, Liu, Tao, Meyer, Clifford A, Eeckhoute, Jérôme, Johnson, David S, Bernstein, Bradley E, ...

MACS performs model-based analysis of ChIP-Seq data generated by short read sequencers.

Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival

Krum, Susan A, Miranda-Carboni, Gustavo A, Hauschka, Peter V, Carroll, Jason S, Lane, Timothy F, Freedman, Leonard P, ...

Estrogen deficiency in menopause is a major cause of osteoporosis in women. Estrogen acts to maintain the appropriate ratio between bone-forming osteoblasts and bone-resorbing osteoclasts in part...

Targeting NF-κB in Waldenstrom macroglobulinemia

Leleu, Xavier, Eeckhoute, Jérôme, Jia, Xiaoying, Roccaro, Aldo M., Moreau, Anne-Sophie, Farag, Mena, ...

The nuclear factor-κB (NF-κB) path-way has been implicated in tumor B-cell survival, growth, and resistance to therapy. Because tumor cells overcome single-agent antitumor activity, we hypothesized...

AKT Alters Genome-Wide Estrogen Receptor α Binding and Impacts Estrogen Signaling in Breast Cancer▿ †

Bhat-Nakshatri, Poornima, Wang, Guohua, Appaiah, Hitesh, Luktuke, Nikhil, Carroll, Jason S., Geistlinger, Tim R., ...

Estrogen regulates several biological processes through estrogen receptor α (ERα) and ERβ. ERα-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT....

Estradiol-regulated microRNAs control estradiol response in breast cancer cells

Bhat-Nakshatri, Poornima, Wang, Guohua, Collins, Nikail R., Thomson, Michael J., Geistlinger, Tim R., Carroll, Jason S., ...

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). E2-inducible proteins c-Myc and...

Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers

Eeckhoute, Jérôme, Lupien, Mathieu, Meyer, Clifford A., Verzi, Michael P., Shivdasani, Ramesh A., Liu, X. Shirley, ...

Selective activity of a specific set of enhancers defines tissue-specific gene transcription. The pioneer factor FOXA1 has been shown to induce functional enhancer competency through chromatin...

Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis

Xia, Xiaobo, Lemieux, Madeleine E., Li, Wei, Carroll, Jason S., Brown, Myles, Liu, X. Shirley, ...

Adaptation to hypoxia is mediated through a coordinated transcriptional response driven largely by hypoxia-inducible factor 1 (HIF-1). We used ChIP-chip and gene expression profiling to identify...

Unique ERα Cistromes Control Cell Type-Specific Gene Regulation

Krum, Susan A., Miranda-Carboni, Gustavo A., Lupien, Mathieu, Eeckhoute, Jerome, Carroll, Jason S., Brown, Myles

Estrogens play an important role in normal physiology and in a variety of pathological states involving diverse tissues including breast and bone. The mechanism by which estrogens exert cell type-...

Target Gene-Specific Regulation of Androgen Receptor Activity by p42/p44 Mitogen-Activated Protein Kinase

Agoulnik, Irina U., Bingman, William E., Nakka, Manjula, Li, Wei, Wang, Qianben, Liu, X. Shirley, ...

Evidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation...