Cis-regulatory Sequence and Co-regulatory Transcription Factor Functions in ERa-mediated Transcriptional Repression PDF Download
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Author: Richard LeRoy Smith
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 78
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Book Description
Estrogens exert numerous actions throughout the human body, targeting healthy tissue while also enhancing the proliferative capacity of breast cancers. Estrogen signaling is mediated by the estrogen receptor (ER), which binds DNA and ultimately affects the expression of adjacent genes. Current understanding of ER-mediated transcriptional regulation is mostly limited to genes whose transcript levels increase following estrogen exposure, though recent studies demonstrate that direct down-regulation of estrogen-responsive genes is also a significant feature of ER action. We hypothesized that difference in cis-regulatory DNA was a factor in determining target gene expression and performed computational and experimental studies to test this hypothesis. From our in silico analyses, we show that the binding motifs for certain transcription factors are enriched in cis-regulatory sequences adjacent to repressed target genes compared to induced target genes, including the motif for RUNX1. In silico analyses were tested experimentally using dual luciferase reporter assays, which indicate that several ER binding sites are estrogen responsive. Mutagenesis of transcription factor motifs (for ER and RUNX1) reduced the response of reporter gene. Further experiments demonstrated that co-recruitment of ER and RUNX1 is necessary for repression of gene expression at some target genes. These findings highlight a novel interaction between ER and RUNX1 and their role in transcriptional repression in breast cancer.
Author: Richard LeRoy Smith
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 78
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Book Description
Estrogens exert numerous actions throughout the human body, targeting healthy tissue while also enhancing the proliferative capacity of breast cancers. Estrogen signaling is mediated by the estrogen receptor (ER), which binds DNA and ultimately affects the expression of adjacent genes. Current understanding of ER-mediated transcriptional regulation is mostly limited to genes whose transcript levels increase following estrogen exposure, though recent studies demonstrate that direct down-regulation of estrogen-responsive genes is also a significant feature of ER action. We hypothesized that difference in cis-regulatory DNA was a factor in determining target gene expression and performed computational and experimental studies to test this hypothesis. From our in silico analyses, we show that the binding motifs for certain transcription factors are enriched in cis-regulatory sequences adjacent to repressed target genes compared to induced target genes, including the motif for RUNX1. In silico analyses were tested experimentally using dual luciferase reporter assays, which indicate that several ER binding sites are estrogen responsive. Mutagenesis of transcription factor motifs (for ER and RUNX1) reduced the response of reporter gene. Further experiments demonstrated that co-recruitment of ER and RUNX1 is necessary for repression of gene expression at some target genes. These findings highlight a novel interaction between ER and RUNX1 and their role in transcriptional repression in breast cancer.
Author: Candace Britton
Publisher:
ISBN: 9781392048436
Category :
Languages : en
Pages : 127
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Book Description
Life often diversifies through changes in gene expression patterns. These patterns evolve via changes in transcriptional regulatory circuits that are determined by transcriptional regulatory proteins and the cis-regulatory sequences they bind in the genome. While it has long been known that changes in cis-regulatory sequences can affect the evolution of gene expression patterns and that transcriptional regulatory proteins can themselves evolve, we know little of how these two types of regulatory changes occur together to generate new circuits. I discerned a stepwise order of evolutionary events in which both regulator protein-coding and cis-regulatory changes were necessary to evolve a new transcriptional regulatory circuit (repression of the a-specific genes by Matalpha2 in yeast). The two changes evolved at separate points in time, millions of years apart. First to evolve were coding-sequence changes in the regulator that formed new protein-protein interaction regions. In one lineage, these new protein-protein interactions became necessary for Matalpha2's ancestral gene regulatory function (repression of the haploid-specific genes with Mata1). In another lineage, millions of years after the coding-sequence changes to Matalpha2, cis-regulatory changes occurred in the a-specific genes, thereby co-opting Matalpha2 for regulation of this new set of target genes. We propose that this evolutionary trajectory is an example of constructive neutral evolution in that Matalpha2's new protein-protein interactions initially had no consequence to the logic of cell-type specific gene regulation, but eventually allowed for the creation of a novel circuit (Chapter 2). In the course of these investigations, I also observed additional coding-sequence changes in the DNA-binding domain of Matalpha2 (Chapter 3), and evolutionary changes in the identities of some of the yeast cell-type specific genes (Chapter 4). The results presented here add to our understanding of the ways in which transcriptional regulatory circuits diversify.
Author: Isabelle S. Peter
Publisher: Academic Press
ISBN: 0124047467
Category : Science
Languages : en
Pages : 461
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Book Description
Genomic Control Process explores the biological phenomena around genomic regulatory systems that control and shape animal development processes, and which determine the nature of evolutionary processes that affect body plan. Unifying and simplifying the descriptions of development and evolution by focusing on the causality in these processes, it provides a comprehensive method of considering genomic control across diverse biological processes. This book is essential for graduate researchers in genomics, systems biology and molecular biology seeking to understand deep biological processes which regulate the structure of animals during development. Covers a vast area of current biological research to produce a genome oriented regulatory bioscience of animal life Places gene regulation, embryonic and postembryonic development, and evolution of the body plan in a unified conceptual framework Provides the conceptual keys to interpret a broad developmental and evolutionary landscape with precise experimental illustrations drawn from contemporary literature Includes a range of material, from developmental phenomenology to quantitative and logic models, from phylogenetics to the molecular biology of gene regulation, from animal models of all kinds to evidence of every relevant type Demonstrates the causal power of system-level understanding of genomic control process Conceptually organizes a constellation of complex and diverse biological phenomena Investigates fundamental developmental control system logic in diverse circumstances and expresses these in conceptual models Explores mechanistic evolutionary processes, illuminating the evolutionary consequences of developmental control systems as they are encoded in the genome
Author: Sarah C. R. Elgin
Publisher: Frontiers in Molecular Biology
ISBN: 9780199638901
Category : Chromatin
Languages : en
Pages : 372
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Book Description
Since publication of the first edition in 1995, there have been significant advances and understanding of chromatin structure and its relation to gene expression. These include a high-resolution structure of the nucleosome core, discovery of the enzymes and complexes that mediate histone acetylation and deacetylation, discovery of novel ATP-dependent chromatin remodeling complexes, new insights into nuclear organization and epigenetic silencing mechanisms. In light of these advances, Chromatin Structure and Gene Expression (2ed.) includes updated chapters and additional material that introduce new concepts in the process of gene regulation in chromatin.
Author: Veronica van Heyningen
Publisher: Academic Press
ISBN: 0080877818
Category : Science
Languages : en
Pages : 415
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Book Description
Long-Range Control of Gene Expression covers the current progress in understanding the mechanisms for genomic control of gene expression, which has grown considerably in the last few years as insight into genome organization and chromatin regulation has advanced. Discusses the evolution of cis-regulatory sequences in drosophila Includes information on genomic imprinting and imprinting defects in humans Includes a chapter on epigenetic gene regulation in cancer
Author: Eric H. Davidson
Publisher: Elsevier
ISBN: 0080455573
Category : Science
Languages : en
Pages : 303
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Book Description
Gene regulatory networks are the most complex, extensive control systems found in nature. The interaction between biology and evolution has been the subject of great interest in recent years. The author, Eric Davidson, has been instrumental in elucidating this relationship. He is a world renowned scientist and a major contributor to the field of developmental biology. The Regulatory Genome beautifully explains the control of animal development in terms of structure/function relations of inherited regulatory DNA sequence, and the emergent properties of the gene regulatory networks composed of these sequences. New insights into the mechanisms of body plan evolution are derived from considerations of the consequences of change in developmental gene regulatory networks. Examples of crucial evidence underscore each major concept. The clear writing style explains regulatory causality without requiring a sophisticated background in descriptive developmental biology. This unique text supersedes anything currently available in the market. The only book in the market that is solely devoted to the genomic regulatory code for animal development Written at a conceptual level, including many novel synthetic concepts that ultimately simplify understanding Presents a comprehensive treatment of molecular control elements that determine the function of genes Provides a comparative treatment of development, based on principles rather than description of developmental processes Considers the evolutionary processes in terms of the structural properties of gene regulatory networks Includes 42 full-color descriptive figures and diagrams
Author: Anita Göndör
Publisher: Academic Press
ISBN: 0128034025
Category : Science
Languages : en
Pages : 498
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Book Description
Chromatin Regulation and Dynamics integrates knowledge on the dynamic regulation of primary chromatin fiber with the 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes. The final chapters discuss the many ways chromatin dynamics can synergize to fundamentally contribute to the development of complex diseases. Chromatin dynamics, which is strategically positioned at the gene-environment interface, is at the core of disease development. As such, Chromatin Regulation and Dynamics, part of the Translational Epigenetics series, facilitates the flow of information between research areas such as chromatin regulation, developmental biology, and epidemiology by focusing on recent findings of the fast-moving field of chromatin regulation. Presents and discusses novel principles of chromatin regulation and dynamics with a cross-disciplinary perspective Promotes crosstalk between basic sciences and their applications in medicine Provides a framework for future studies on complex diseases by integrating various aspects of chromatin biology with cellular metabolic states, with an emphasis on the dynamic nature of chromatin and stochastic principles Integrates knowledge on the dynamic regulation of primary chromatin fiber with 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes
Author:
Publisher: Academic Press
ISBN: 0128170735
Category : Science
Languages : en
Pages : 552
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Book Description
Echinoderms, Volume 151, the latest release in the Methods in Cell Biology series, highlights advances in the field, with this update presenting chapters on Echinoderm Genome Databases, analysis of gene regulatory networks, using ATAC-seq and RNA-seq to increase resolution in GRN connectivity, multiplex cis-regulatory analysis, experimental approaches GRN/signal pathways, BACs, analysis of chromatin accessibility using ATAC-seq, analysis of sea urchin proteins /Click IT, CRISPR/Cas9-mediated genome editing in sea urchins, super-resolution and in toto imaging of echinoderm embryos, and methods for analysis of intracellular ion signals in sperm, eggs and embryos. Presents clear, concise protocols provided by experts who have established the echinoderms as a model systems Highlights new advances in the field, with this update presenting interesting chapters on echinoderms
Author: Renato Paro
Publisher: Springer Nature
ISBN: 3030686701
Category : Science
Languages : en
Pages : 215
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Book Description
This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Author: Rajesh K. Gaur
Publisher: CRC Press
ISBN: 1420008706
Category : Science
Languages : en
Pages : 440
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Book Description
New Findings Revolutionize Concepts of Gene FunctionEndogenous small RNAs have been found in various organisms, including humans, mice, flies, worms, fungi, and bacteria. Furthermore, it's been shown that microRNAs acting as cellular rheostats have the ability to modulate gene expression. In higher eukaryotes, microRNAs may regulate as much as 50 p
