Expression And Developmental Control Of The Human Embryonic Beta Globin Gene In Transgenic Mice

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Expression And Developmental Control Of The Human Embryonic Beta Globin Gene In Transgenic Mice

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Author : Diana Mouhan Shih
language : en
Publisher:
Release Date : 1992

Expression And Developmental Control Of The Human Embryonic Beta Globin Gene In Transgenic Mice written by Diana Mouhan Shih and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1992 with Gene expression categories.

Developmental Control Of Globin Gene Expression

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Author : George Stamatoyannopoulos
language : en
Publisher:
Release Date : 1987

Developmental Control Of Globin Gene Expression written by George Stamatoyannopoulos and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1987 with Science categories.

The Study Of The Regulatory Elements Of The Human 221 Globin Gene

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Author : Ping-Kei Chan
language : en
Publisher: Open Dissertation Press
Release Date : 2017-01-26

The Study Of The Regulatory Elements Of The Human 221 Globin Gene written by Ping-Kei Chan and has been published by Open Dissertation Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-01-26 with categories.

This dissertation, "The Study of the Regulatory Elements of the Human {221}-globin Gene" by Ping-kei, Chan, 陳炳基, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled THE STUDY OF THE REGULATORY ELEMENTS OF THE HUMAN β-GLOBIN GENE Submitted by Chan Ping Kei For the degree of Doctor of Philosophy at The University of Hong Kong in June 2005 The human β-globin locus contains five developmentally regulated β-like globin G A genes arranged in the order of their developmental expression (5' ε-γ-γ-δ-β 3'). All five genes are regulated by an element located far upstream of the locus called the Locus Control Region (LCR). High level of β-globin gene expression is regulated by the LCR which consists of erythroid specific hypersensitive sites HS1 to HS5. Transcriptional regulation of the globin genes occurs through the cooperation of the LCR, the promoters of the globin genes and the interactions of trans-acting proteins. Recent studies show that activation of the β-globin locus involves the spatial formation of a LCR holocomplex that directly interacts with the transcribed genes. This complex is called the Active Chromatin Hub (ACH) (Palstra et al., 2003;Drissen et al., 2004). The objective of this project is to study the functional roles of two regulatory elements, namely, hypersensitive site 5 (HS5) of the LCR and the (AC) (AT) T motif n x y at the promoter of the β-globin gene. We study the enhancer blocking function of HS5 in transgenic mice by analyzing the conformational change in the context of the β-gene locus using the Chromatin Conformation Capture (3C) technique. The results show that HS5 functions as an enhancer blocking element in embryonic blood but not in adult erythroid cells. Interestingly, when HS5 is deleted form the locus, elements located upstream of the LCR are able to interact with the downstream regulatory elements within the β-globin gene locus. These results suggest that HS5 is a developmental stage specific border element. We determine whether CTCF, the only defined insulator protein in mammalian cells, binds to HS5 by using the CTCF-Chromatin immunoprecipitation (ChIP) assay. Our results demonstrate that CTCF binds to human HS5 and may mediate enhancer blocking activity in erythroid cell in vivo. In the second part of the thesis, we have examined the (AC) (AT) T motif n x y residing -530bp 5' upstream of the β-globin gene in Chinese thalassaemic patients. This motif is a putative binding site for a repressor protein, namely beta protein 1 (BP1) (Berg et al., 1989). It has been shown that variations in the (AC) (AT) T n x y repeats affect the binding affinity of BP1 thereby altering the expression of the β-globin gene. Eight different configurations of this repeat motif are identified in our population of Chinese β-thalassaemia patients in Hong Kong. A novel (AC) (AT) T 3 7 5 motif is identified among the thalassaemia patients and its influence in β-globin gene expression is studied using stable transfection assay in murine erythroleukemia (MEL) cells. Our results demonstrate that this motif has moderately strong repressor effect on the expression of the cis-linked β-globin gene. This may be due to the higher affinity of BP1 for the motif resulting in the suppression of the transcription of the β-globin gene. We conclude that the proper developmental expression pattern of the β-like globin gene cluster is absolutely dependent on the presence of both the LCR and the proximal cis-regulatory elements of the globin gene. DOI: 10.5353/th_b

Disorders Of Hemoglobin

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Author : Martin H. Steinberg
language : en
Publisher: Cambridge University Press
Release Date : 2009-08-17

Disorders Of Hemoglobin written by Martin H. Steinberg and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-08-17 with Medical categories.

Completely revised new edition of the definitive reference on disorders of hemoglobin.

Regulation Of The Mouse And Human Beta Globin Genes By Kr Ppel Like Transcription Factors Klf1 And Klf2

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Author : Yousef Nassir Alhashem
language : en
Publisher:
Release Date : 2012

Regulation Of The Mouse And Human Beta Globin Genes By Kr Ppel Like Transcription Factors Klf1 And Klf2 written by Yousef Nassir Alhashem and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.

Krüppel-like factors KLF1 and KLF2 are closely related transcription factors with three zinc finger domains in their carboxy-termini. KLF1 (erythroid Krüppel-like factor, or EKLF) plays essential roles in embryonic and adult erythropoiesis. KLF2 is a positive regulator of the mouse and human embryonic [beta]- globin genes. KLF1 and KLF2 have overlapping roles in embryonic erythropoiesis, as demonstrated using single and double knockout (KO) mouse models. Ablation of the KLF1 or KLF2 gene causes embryonic lethality, and double KO embryos are more anemic and die sooner than either single KO. We have shown that KLF1 and KLF2 positively regulate the human [epsilon]- (embryonic) and [gamma]-globin (fetal) genes during embryonic erythropoiesis. Chromatin immunoprecipitation assays (ChIP) show that KLF1 and KLF2 bind to the promoters of the human [epsilon]- and [gamma]-globin genes, the mouse embryonic Ey- and [beta]h1-globin genes, and also to the [beta]-globin locus control region (LCR) in mouse embryonic erythroid cells. ChIP assays show that KLF1 but not KLF2 ablation results in abnormal histone modifications in the [beta]-globin locus in mouse embryonic erythroid cells. H3K9Ac and H3K4me3, which correlate with open chromatin and active transcription, are both reduced in KLF1-/- primitive erythroid cells. Human CD34+ hematopoietic stem cells obtained from umbilical cord blood were in vitro differentiated along the erythroid lineage. ChIP assays indicate that both KLF1 and KLF2 bind to the promoter of [gamma]-globin gene in this fetal erythroid model. KLF1 knockdown in these cells affects mainly adult [beta]- globin gene expression. However, the decrease in [beta]- globin gene expression in KLF1 knockdown also affects the ratio of [gamma]- to [beta]- globin in these cells. H3K9Ac and H3K4me3 were decreased only at the [beta]- globin gene which coincides with lower recruitment of RNA polymerase II and its active form, RNA polymerase II phospho-serine 2. In conclusion, we showed using mouse primitive erythroid cells and cord blood definitive cells that KLF1 and KLF2 coordinate the regulation of the mouse and human [beta]- globin genes by direct binding to the promoters and LCR in the [beta]- globin locus. In conclusion, cord blood hematopoietic cells could serve as a complimentary system in addition to the transgenic mouse models to study the regulation of [gamma]- globin gene expression.

The Molecular Basis Of Blood Diseases

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Author : George Stamatoyannopoulos
language : en
Publisher: Saunders
Release Date : 2001

The Molecular Basis Of Blood Diseases written by George Stamatoyannopoulos and has been published by Saunders this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001 with Medical categories.

The superb Third Edition of this popular text covers all the recent groundbreaking developments which have taken place in this field. Comprehensively revised, it presents all the latest findings on the molecular bases of blood cell functions and disease mechanisms and the impact of these discoveries on the state of medicine. This edition includes new chapters such as signaling and antigen presentation by B-lymphocytes, molecular oncogenesis and more!

The Thalassaemia Syndromes

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Author : David J. Weatherall
language : en
Publisher: John Wiley & Sons
Release Date : 2008-04-30

The Thalassaemia Syndromes written by David J. Weatherall and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-04-30 with Medical categories.

In the new edition of this successful and authoritative book, the thalassaemias are reviewed in detail with respect to their clinical features, cellular pathology, molecular genetics, prevention and treatment. It is aimed at specialists in haematology in the laboratory or clinical setting, particularly in areas where thalassaemia is common either in the native population or in immigrant communities. The fourth edition has been both updated and re-organized. Three new chapters have been added on the link between alpha-thalassaemia and mental retardation, on avoidance and population control and on global epidemiology. Considerable emphasis is placed on molecular pathology reflecting the huge burst of information to have come out of this field in the last few years.

Globin Gene Expression And Hematopoietic Differentiation

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Author : George Stamatoyannopoulos
language : en
Publisher:
Release Date : 1983

Globin Gene Expression And Hematopoietic Differentiation written by George Stamatoyannopoulos and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1983 with Science categories.

Cellular And Molecular Regulation Of Hemoglobin Switching

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Author : George Stamatoyannopoulos
language : en
Publisher: Grune & Stratton, Incorporated
Release Date : 1979

Cellular And Molecular Regulation Of Hemoglobin Switching written by George Stamatoyannopoulos and has been published by Grune & Stratton, Incorporated this book supported file pdf, txt, epub, kindle and other format this book has been release on 1979 with Medical categories.

Human Hemoglobins

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Author : Howard Franklin Bunn
language : en
Publisher: W.B. Saunders Company
Release Date : 1977

Human Hemoglobins written by Howard Franklin Bunn and has been published by W.B. Saunders Company this book supported file pdf, txt, epub, kindle and other format this book has been release on 1977 with Medical categories.

Since the dawn of the era of molecular biology, hemoglobin has been subjected to more scrutiny than any other protein, and Bunn, Forget, and Ranney can each lay claim to major contributions to the saga of hemoglobin. Their well-organized, comprehensive, and superbly illustrated work is an excellent review of the abnormal hemoglobin field. Early chapters deal with the structure and function of human hemoglobin and the way in which this is modified in various disease states. Later sections deal with the various structural hemoglobin variants and their associated clinical manifestations, the thalassaemias, and the acquired disorders of hemoglobin. The sections that deal with the modification of hemoglobin function in various disease states are particularly good. The book contains an extensive and up-to-date bibliography and is remarkably free from errors of fact or type--the best standard of reference on the subject as of the year 1977.