Transcriptional control of globin gene switching during vertebrate development

Baron, Margaret H.

doi:10.1016/s0167-4781(96)00195-9

Cited by 45 publications

(32 citation statements)

References 140 publications

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“…In addition, gestation length may be influenced by Hb switching. This switching is regulated by a "molecular clock" in that factors specific to fetal developmental stages are believed to control the sequential production of different haemoglobins (Baron, 1997). In the case of the roan antelope, decreasing Hb concentrations during the fetal/adult Hb switching period will therefore, at a specific gestational age, stimulate a fetal hypoxic stress response that may contribute to the initiation of partus (Liggins et al, 1973).…”

Section: Discussionmentioning

confidence: 99%

Erythrocyte Morphology and Haemoglobin Types of Neonatal Roan Antelopes (Hippotragus equinus) with Hypochromic Poikilocytic Anaemia

Parsons

Penzhorn

Reyers³

et al. 2006

Journal of Comparative Pathology

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SummaryNeonatal, poikilocytic anaemia in some members of the Hippotragini has previously been documented but not fully investigated. This study was undertaken to describe the erythrocyte morphology of roan antelopes (Hippotragus equinus) during the first 4 weeks after birth and to identify aspects of haemoglobin (Hb) production that might be implicated in this syndrome. Twenty-nine roan antelope calves were sampled on, or close to, 1, 7, 14 and 28 days after birth. Erythrocyte morphology was characterized, and microhaematocrit values and Hb parameters determined, for each sampling occasion. Findings indicated a significant change in erythrocyte morphology during the neonatal period and two haemoglobin types, fetal and adult, were identified. The perinatal onset of adult Hb synthesis was delayed relative to the termination of fetal Hb production, resulting in the observed anaemia. Haemoglobin concentration and erythrocyte morphology were significantly correlated. These findings suggest an intimate relationship between Hb synthesis and the observed poikilocytosis. An imbalance in the synthesis of the α-and ß-globin chains of Hb (a thalassaemia) may prove to be the underlying pathophysiology of this syndrome. Article Outline

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Section: Discussionmentioning

confidence: 99%

Erythrocyte Morphology and Haemoglobin Types of Neonatal Roan Antelopes (Hippotragus equinus) with Hypochromic Poikilocytic Anaemia

Parsons

Penzhorn

Reyers³

et al. 2006

Journal of Comparative Pathology

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“…The ␤-globin gene is expressed to a small extent in the fetus but predominates after birth in bone marrow (21,23). In this complex process of globin switching, it is currently not clear what roles are played by chromatin structures (2,10) and by interactions between the genes and the LCR and transcription factors (5). The protamine 2 gene was studied as an example of a gene which is transcribed at the stage when histones are being displaced from spermatids but thereafter remains silent in the embryo (19).…”

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confidence: 99%

Histone- and Protamine-DNA Association: Conservation of Different Patterns within the β-Globin Domain in Human Sperm

Gardiner-Garden

Ballesteros

Gordon

et al. 1998

Molecular and Cellular Biology

143

105

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Most DNA in human sperm is bound to highly basic proteins called protamines, but a small proportion is complexed with histones similar to those found in active chromatin. This raises the intriguing possibility that histones in sperm are marking sets of genes that will be preferentially activated during early development. We have examined the chromatin structure of members of the ␤-globin gene family, which are expressed at different times in development, and the protamine 2 gene, which is expressed in spermatids prior to the widespread displacement of histones by transition proteins. The genes coding for and ␥ globin, which are active in the embryonic yolk sac, contain regions which are histone associated in the sperm. No histoneassociated regions are present at the sites tested within the ␤-and ␦-globin genes which are silent in the embryonic yolk sac. The trends of histone or protamine association are consistent for samples from the same person, and no significant between-subject variations in these trends are found for 13 of the 15 fragments analyzed in the two donors. The results suggest that sperm chromatin structures are generally similar in different men but that the length of the histone-associated regions can vary. The association of sperm DNA with histones or protamines sometimes changes within as little as 400 bp of DNA, suggesting that there is fine control over the retention of histones.Complex rearrangements of the sperm chromatin occur during mammalian spermatogenesis. In the elongating spermatids, the histones associated with the DNA are displaced by transition proteins, which in turn are replaced by protamines. As a result of this process, the chromatin in the spermatozoa is highly condensed (17). In human sperm, approximately 15% of the DNA remains associated with histones in a sequence-specific manner (12,25). The histones in sperm chromatin are a subset of the histones found in somatic chromatin (13), and they form nucleosomes which are more closely packed than those found in somatic cells (4). Histone H1 is absent, histone H2 takes the form of two minor variants, called H2A.X and H2A.Z, and the histones H3 and H4 are extensively acetylated (13). Absence of histone H1 and acetylation of histones are both features of active chromatin (28,29). This has led to the suggestion that histones in sperm could influence which genes are first transcribed after fertilization (12).To explore the impact of sperm chromatin on temporal gene regulation, we analyzed the ␤-globin family of genes which are transcribed at different times during development. The ␤-globin locus from 5Ј to 3Ј consists of the locus control region (LCR) and the ε-, G ␥-, A ␥-, ␦-, and ␤-globin genes. Only the ε-and ␥-globin genes are transcribed in the primitive erythroblasts in the embryonic yolk sac which differentiates at 3 weeks of gestation. The expression of the ␥-globin gene predominates during the fetal period when the site of erythropoiesis shifts to the definitive erythroblasts in the fetal liver. The ␦-globin gene product i...

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“…The first stage-specific switch in globin gene transcription involves both the ␣-and ␤-globin loci. Primitive erythroid cells formed in the blood islands of the yolk sac during the first few weeks of human gestation produce the embryonic globins ε (␤-like) and (␣-like) (3,45). Around the sixth week of gestation, the site of erythropoiesis shifts to the fetal liver, where definitive erythroid cells express the ␥ (␤-like)-and ␣-globin genes (44).…”

mentioning

confidence: 99%

“…The second hemoglobin switching event occurs around the time of birth and involves only the ␤-globin locus. Coincident with a shift in the site of erythropoiesis to the bone marrow, the fetal ␤-like globin gene (␥) is downregulated and the adult ␤-globin gene is activated (3,45). Although hemoglobin switching has been studied extensively, the molecular mechanisms underlying stage-specific expression of the globin genes are not completely understood (discussed in reference 3).…”

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confidence: 99%

The HMG Domain Protein SSRP1/PREIIBF Is Involved in Activation of the Human Embryonic β-Like Globin Gene

Dyer

Hayes

Baron

1998

Molecular and Cellular Biology

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The human embryonic ␤-like globin (-globin) gene is expressed in primitive erythroid cells of the yolk sac during the first few weeks of development. We have previously shown that developmental stage-specific expression of the -globin gene is mediated by multiple positive and negative regulatory elements upstream of the start of transcription. Of particular interest is one positive regulatory element, PRE II, that works together with other elements (PRE I and PRE V) to confer developmental stage-and/or tissue-specific expression on a minimal promoter. An ϳ85-to 90-kDa PRE II binding factor (PREIIBF) was identified in the nuclei of erythroid cells and shown to bind specifically to a novel 19-bp region within PRE II; binding of this protein to PRE II resulted in bending of the target DNA and was required for promoter activation. In this report, we present the cDNA expression cloning of PREIIBF. The cDNA encodes a previously identified member of the HMG domain family of DNA binding proteins termed SSRP1. By a number of biochemical and immunological criteria, recombinant SSRP1 appears to be identical to the PREII binding factor from erythroid nuclei. A hallmark of HMG domain proteins is their ability to bend their target DNAs; therefore, as we speculated previously, DNA bending by SSRP1/PREIIBF may contribute to the mechanism by which PRE II synergizes with other regulatory elements located upstream and downstream. In contrast with reports from other investigators, we demonstrate that SSRP1 binds DNA with clear sequence specificity. Moreover, we show that SSRP1/PREIIBF lacks a classical activation domain but that binding by this protein to PRE II is required for activation of a minimal promoter in stable erythroid cell lines. These studies provide the first evidence that SSRP1 plays a role in transcriptional regulation. SSRP1/PREIIBF may serve an architectural function by helping to coordinate the assembly of a multiprotein complex required for stage-specific regulation of the human -globin gene.

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Transcriptional control of globin gene switching during vertebrate development

Cited by 45 publications

References 140 publications

Erythrocyte Morphology and Haemoglobin Types of Neonatal Roan Antelopes (Hippotragus equinus) with Hypochromic Poikilocytic Anaemia

Erythrocyte Morphology and Haemoglobin Types of Neonatal Roan Antelopes (Hippotragus equinus) with Hypochromic Poikilocytic Anaemia

Histone- and Protamine-DNA Association: Conservation of Different Patterns within the β-Globin Domain in Human Sperm

The HMG Domain Protein SSRP1/PREIIBF Is Involved in Activation of the Human Embryonic β-Like Globin Gene

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