scholarly journals Persistent Changes in Gene Expression Induced by Estrogen and Progesterone in the Rat Mammary Gland

2001 ◽  
Vol 15 (11) ◽  
pp. 1993-2009 ◽  
Author(s):  
Melanie R. Ginger ◽  
Maria F. Gonzalez-Rimbau ◽  
Jason P. Gay ◽  
Jeffrey M. Rosen
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Cell Fate ◽  
Noncoding Rna ◽  
Previous Treatment ◽  
Hormone Treatment ◽  
Subtractive Hybridization ◽  
Epidemiological Studies ◽  
Altered Expression ◽  
Hormonal Milieu

Abstract Epidemiological studies have consistently shown that an early full-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland, leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization to identify genes that are persistently up-regulated in the glands of E- and progesterone (P)-treated Wistar-Furth rats 28 d after steroid hormone treatment compared with age-matched virgins. Using this approach, a number of genes displaying persistent altered expression in response to previous treatment with E and P were identified. Two markers have been characterized in greater detail: RbAp46 and a novel gene that specifies a noncoding RNA (designated G.B7). Both were persistently up-regulated in the lobules of the regressed gland and required previous treatment with both E and P for maximal persistent expression. RbAp46 has been implicated in a number of complexes involving chromatin remodeling, suggesting a mechanism whereby epigenetic factors responsible for persistent changes in gene expression may be related to the determination of cell fate. These results provide the first support at the molecular level for the hypothesis that hormone-induced persistent changes in gene expression are present in the involuted mammary gland.

scholarly journals Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Brian Dean ◽  
Elizabeth Scarr
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Ability ◽  
Noncoding Rna ◽  
Wild Type Mouse ◽  
Amyloid Precursor Protein Processing ◽  
Frontal Pole ◽  
Altered Expression ◽  
Receptor Knockout Mouse

AbstractPostmortem and neuroimaging studies show low levels of cortical muscarinic M1 receptors (CHRM1) in patients with schizophrenia which is significant because CHRM signalling has been shown to change levels of gene expression and cortical gene expression is altered in schizophrenia. We decided to identify CHRM1-mediated changes in cortical gene expression by measuring levels of RNA in the cortex of the Chrm1−/− mouse (n = 10), where there would be no signalling by that receptor, and in wild type mouse (n = 10) using the Affymetrix Mouse Exon 1.0 ST Array. We detected RNA for 15,501 annotated genes and noncoding RNA of which 1,467 RNAs were higher and 229 RNAs lower in the cortex of the Chrm1−/− mouse. Pathways and proteins affected by the changes in cortical gene expression in the Chrm1−/− are linked to the molecular pathology of schizophrenia. Our human cortical gene expression data showed 47 genes had altered expression in Chrm1−/− mouse and the frontal pole from patients with schizophrenia with the change in expression of 44 genes being in opposite directions. In addition, genes with altered levels of expression in the Chrm1−/− mouse have been shown to affect amyloid precursor protein processing which is associated with the pathophysiology of Alzheimer’s disease, and 69 genes with altered expression in the Chrm1−/− mouse are risk genes associated with human cognitive ability. Our findings argue CHRM1-mediated changes in gene expression are relevant to the pathophysiologies of schizophrenia and Alzheimer’s disease and the maintenance of cognitive ability in humans.

scholarly journals Glucocorticoid-Induced Impairment of Mammary Gland Involution Is Associated with STAT5 and STAT3 Signaling Modulation

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5730-5740 ◽  
Author(s):  
Paola Y. Bertucci ◽  
Ana Quaglino ◽  
Andrea G. Pozzi ◽  
Edith C. Kordon ◽  
Adali Pecci
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Epithelial Cell ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Mammary Epithelium ◽  
Hormone Treatment ◽  
Signal Transducer ◽  
Stat3 Signaling ◽  
Epithelial Cell Apoptosis

The mammary epithelium undergoes cyclical periods of cellular proliferation, differentiation, and regression. During lactation, the signal transducer and activator of transcription factor (STAT)-5A and the glucocorticoid receptor (GR) synergize to induce milk protein expression and also act as survival factors. During involution, STAT3 activation mediates epithelial cell apoptosis and mammary gland remodeling. It has been shown that the administration of glucocorticoids at weaning prevents epithelial cell death, probably by extracellular matrix breakdown prevention. Our results show that the synthetic glucocorticoid dexamethasone (DEX) modulates STAT5A and STAT3 signaling and inhibits apoptosis induction in postlactating mouse mammary glands, only when administered within the first 48 h upon cessation of suckling. DEX administration right after weaning delayed STAT5A inactivation and degradation, preserving gene expression of target genes as β-casein (bcas) and prolactin induced protein (pip). Weaning-triggered GR down-regulation is also delayed by the hormone treatment. Moreover, DEX administration delayed STAT3 activation and translocation into epithelial cells nuclei. In particular, DEX treatment impaired the increment in gene expression of signal transducer subunit gp130, normally up-regulated from lactation to involution and responsible for STAT3 activation. Therefore, the data shown herein indicate that glucocorticoids are able to modulate early involution by controlling the strong cross talk that GR, STAT5, and STAT3 pathways maintains in the mammary epithelium.

scholarly journals Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis

Blood ◽  
2017 ◽  
Vol 130 (18) ◽  
pp. 1965-1975 ◽  
Author(s):  
Juan R. Alvarez-Dominguez ◽  
Harvey F. Lodish
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Noncoding Rna ◽  
Effector Proteins ◽  
Protein Targets ◽  
Ability To Act ◽  
Coordinate Gene Expression ◽  
Multiple Levels ◽  
And Function ◽  
Influence Gene Expression

Abstract Long noncoding RNAs (lncRNAs) are increasingly recognized as vital components of gene programs controlling cell differentiation and function. Central to their functions is an ability to act as scaffolds or as decoys that recruit or sequester effector proteins from their DNA, RNA, or protein targets. lncRNA-modulated effectors include regulators of transcription, chromatin organization, RNA processing, and translation, such that lncRNAs can influence gene expression at multiple levels. Here we review the current understanding of how lncRNAs help coordinate gene expression to modulate cell fate in the hematopoietic system. We focus on a growing number of mechanistic studies to synthesize emerging principles of lncRNA function, emphasizing how they facilitate diversification of gene programming during development. We also survey how disrupted lncRNA function can contribute to malignant transformation, highlighting opportunities for therapeutic intervention in specific myeloid and lymphoid cancers. Finally, we discuss challenges and prospects for further elucidation of lncRNA mechanisms.

scholarly journals A noncoding RNA is a potential marker of cell fate during mammary gland development

2006 ◽  
Vol 103 (15) ◽  
pp. 5781-5786 ◽  
Author(s):  
M. R. Ginger ◽  
A. N. Shore ◽  
A. Contreras ◽  
M. Rijnkels ◽  
J. Miller ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cell Fate ◽  
Noncoding Rna ◽  
Mammary Gland Development ◽  
Potential Marker ◽  
Gland Development

scholarly journals MicroRNAs in the development and neoplasia of the mammary gland

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1018
Author(s):  
Manoj Kumar Jena
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Mammary Gland ◽  
Cancer Progression ◽  
Developmental Stages ◽  
Mammary Epithelial Cells ◽  
Tumour Progression ◽  
Mammary Epithelial ◽  
Altered Expression

Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2) signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes. Oncogenic miRs like miR-21, miR-221, and miR-210 are overexpressed in triple negative breast cancer cases which can be diagnostic biomarker for this subtype of cancer.  This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages) and their involvement in breast cancer progression. Further studies in this area will help us to understand the molecular details of mammary gland biology, as well as miRs that could be therapeutic targets of breast cancer.

Roles of Regulatory RNAs in Nutritional Control

2020 ◽  
Vol 40 (1) ◽  
pp. 77-104
Author(s):  
Elizabeth M. McNeill ◽  
Kendal D. Hirschi
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Small Rnas ◽  
Noncoding Rna ◽  
Small Cell ◽  
Altered Expression ◽  
Nutritional Interventions ◽  
Metabolic Genes ◽  
Regulatory Rnas ◽  
Dietary Bioactive Compounds

Small RNAs (sRNAs), including microRNAs (miRNAs), are noncoding RNA (ncRNA) molecules involved in gene regulation. sRNAs play important roles in development; however, their significance in nutritional control and as metabolic modulators is still emerging. The mechanisms by which diet impacts metabolic genes through miRNAs remain an important area of inquiry. Recent work has established how miRNAs are transported in body fluids often within exosomes, which are small cell-derived vesicles that function in intercellular communication. The abundance of other recently identified ncRNAs and new insights regarding ncRNAs as dietary bioactive compounds could remodel our understanding about how foods impact gene expression. Although controversial, some groups have shown that dietary RNAs from plants and animals (i.e., milk) are functional in consumers. In the future, regulating sRNAs either directly through dietary delivery or indirectly by altered expression of endogenous sRNA may be part of nutritional interventions for regulating metabolism.

scholarly journals Characterization of Stat5a and Stat5b Homodimers and Heterodimers and Their Association with the Glucocortiocoid Receptor in Mammary Cells

1998 ◽  
Vol 18 (4) ◽  
pp. 1783-1792 ◽  
Author(s):  
Nathalie Cella ◽  
Bernd Groner ◽  
Nancy E. Hynes
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Milk Protein ◽  
Protein Gene ◽  
Hormone Treatment ◽  
Functional Coupling ◽  
Mammary Cells ◽  
Milk Protein Gene ◽  
Lactogenic Hormone ◽  
Milk Protein Gene Expression

ABSTRACT The lactogenic hormones, i.e., prolactin and glucocorticoids, act in concert to stimulate transcription factors responsible for hormone-dependent milk protein gene expression. In the mammary gland, prolactin activates Stat5a and Stat5b and glucocorticoids activate the glucocorticoid receptor (GR). Immunoprecipitation experiments revealed that in mammary cells, Stat5a, Stat5b, and the GR are physically associated in vivo. The association is not dependent on lactogenic hormone treatment and is evident at all stages of mammary gland development. Immunodepletion experiments indicated that a fraction of GR and Stat5 proteins are not associated, suggesting that there are different intracellular pools of these proteins. Lactogenic hormone treatment of HC11 mammary cells resulted in tyrosine phosphorylation of Stat5a and Stat5b, dimerization, and rapid nuclear translocation of both Stat5 proteins. Following hormone treatment, Stat5a-Stat5b heterodimers were detected by their coimmunoprecipitation. In addition, immunodepletion experiments followed by gel shift analyses revealed the presence of active Stat5a and Stat5b homodimers. In mammary cells, Stat5b homodimers are less abundant than Stat5a homodimers. Although the GR does not bind the Stat5 DNA binding site directly, it could be detected with the Stat5-DNA complex. These results suggest that glucocorticoids affect milk protein gene expression via association of the GR with Stat5. Thus, there is a functional coupling between Stat-dependent and nuclear hormone receptor-dependent gene transcription.

A mini-review: microRNA in arthritis

2011 ◽  
Vol 43 (10) ◽  
pp. 566-570 ◽  
Author(s):  
Tomoyuki Nakasa ◽  
Yoshihiko Nagata ◽  
Keiichiro Yamasaki ◽  
Mitsuo Ochi
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Mononuclear Cells ◽  
Expression Patterns ◽  
Joint Destruction ◽  
Synovial Cell ◽  
Specific Expression ◽  
Peripheral Blood Mononuclear ◽  
Altered Expression

MicroRNA (miRNA) is a class of noncoding RNA that exhibits tissue- or developmental stage-specific expression patterns and negatively regulates gene expression. MiRNAs play an important role in human diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). OA is characterized by the progressive destruction of articular cartilage, and several miRNAs exhibit altered expression, playing a role in regulating gene expression in OA pathogenesis, especially in catabolic factors such as matrix metalloproteinases (MMP) and aggrecanases. RA is an autoimmune disease that is characterized by irreversible joint destruction due to chronic synovial inflammation. MiRNAs play an important role in inflammatory response, synovial cell proliferation, and production of MMPs in RA synovial tissues. The expression level of several miRNAs in peripheral blood mononuclear cells correlates with RA disease activity. Recently, therapeutic trials aimed at targeting miRNA in vivo have been conducted. Targeting miRNA will enable a new advanced strategy toward arthritis treatment.

scholarly journals Altered gene expression in slc4a11−/− mouse cornea highlights SLC4A11 roles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bernardo V. Alvarez ◽  
Marilyse Piché ◽  
Carolin Aizouki ◽  
Fariha Rahman ◽  
Jonathan M. J. Derry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Energy Metabolism ◽  
Cell Fate ◽  
Ion Homeostasis ◽  
Corneal Dystrophy ◽  
Mrna Levels ◽  
Altered Expression ◽  
Reverse Transcription Pcr ◽  
Extracellular Region

AbstractSLC4A11 is a H+/NH3/water transport protein, of corneal endothelial cells. SLC4A11 mutations cause congenital hereditary endothelial dystrophy and some cases of Fuchs endothelial corneal dystrophy. To probe SLC4A11’s roles, we compared gene expression in RNA from corneas of 17-week-old slc4a11−/− (n = 3) and slc4a11+/+ mice (n = 3) and subjected to RNA sequencing. mRNA levels for a subset of genes were also assessed by quantitative real-time reverse transcription PCR (qRT RT-PCR). Cornea expressed 13,173 genes, which were rank-ordered for their abundance. In slc4a11−/− corneas, 100 genes had significantly altered expression. Abundant slc14a1 expression, encoding the urea transporter UT-A, suggests a significant role in the cornea. The set of genes with altered expression was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, revealing that alterations clustered into extracellular region, cytoskeleton, cell adhesion and plasma membrane functions. Gene expression changes further clustered into classes (with decreasing numbers of genes): cell fate and development, extracellular matrix and cell adhesion, cytoskeleton, ion homeostasis and energy metabolism. Together these gene changes confirm earlier suggestions of a role of SLC4A11 in ion homeostasis, energy metabolism, cell adhesion, and reveal an unrecognized SLC4A11 role in cytoskeletal organization.

scholarly journals Transcription levels of a long noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast

2019 ◽  
Author(s):  
Fabien Moretto ◽  
N. Ezgi Wood ◽  
Minghao Chia ◽  
Cai Li ◽  
Nicholas M. Luscombe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Transcriptional Repression ◽  
Noncoding Rna ◽  
Histone H3 ◽  
Noncoding Rnas ◽  
Enhancer Rna ◽  
Regulatory Circuit ◽  
In Cis ◽  
Histone Exchange

ABSTRACTMany long noncoding RNAs (lncRNAs) act in cis through transcription-coupled chromatin alterations that drive changes in local gene expression. How some cis-acting lncRNAs promote and others repress gene expression remains poorly understood. Here we report that in S. cerevisiae transcription levels of the lncRNA IRT2, located upstream in the promoter of the inducer of meiosis gene, regulate opposing chromatin and transcription states. Low IRT2 transcription displays enhancer RNA-like features. At these levels, IRT2 promotes histone exchange delivering acetylated histone H3 lysine 56 to chromatin thereby facilitating recruitment of a transcription factor and consequently activating transcription. Conversely, increasing IRT2 transcription enhances chromatin assembly and transcriptional repression. The opposing functions of IRT2 direct a regulatory circuit, which ensures that cells expressing opposite, but not one of either, mating-type loci enter meiosis. Our data demonstrate that the transcription levels of an lncRNA are key to controlling gene expression and cell fate outcomes.

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