Use of Yeast Artificial Chromosomes (YACs) in Studies of Mammalian Development: Production of Beta-globin Locus YAC Mice Carrying Human Globin Developmental Mutants

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 Jun 6

PMID 7539923

Citations 49

Authors

K R Peterson

Q L Li

C H Clegg

T Furukawa

P A Navas

E J Norton

T G Kimbrough

G Stamatoyannopoulos

Affiliations

Soon will be listed here.

Abstract

To test whether yeast artificial chromosomes (YACs) can be used in the investigation of mammalian development, we analyzed the phenotypes of transgenic mice carrying two types of beta-globin locus YAC developmental mutants: (i) mice carrying a G-->A transition at position -117 of the A gamma gene, which is responsible for the Greek A gamma form of hereditary persistence of fetal hemoglobin (HPFH), and (ii) beta-globin locus YAC transgenic lines carrying delta- and beta-globin gene deletions with 5' breakpoints similar to those of deletional HPFH and delta beta-thalassemia syndromes. The mice carrying the -117 A gamma G-->A mutation displayed a delayed gamma- to beta-globin gene switch and continued to express A gamma-globin chains in the adult stage of development as expected for carriers of Greek HPFH, indicating that the YAC/transgenic mouse system allows the analysis of the developmental role of cis-acting motifs. The analysis of mice carrying 3' deletions first provided evidence in support of the hypothesis that imported enhancers are responsible for the phenotypes of deletional HPFH and second indicated that autonomous silencing is the primary mechanism for turning off the gamma-globin genes in the adult. Collectively, our results suggest that transgenic mice carrying YAC mutations provide a useful model for the analysis of the control of gene expression during development.

Citing Articles

Limitations of mouse models for sickle cell disease conferred by their human globin transgene configurations.

Woodard K, Doerfler P, Mayberry K, Sharma A, Levine R, Yen J Dis Model Mech. 2022; 15(6).

PMID: 35793591 PMC: 9277148. DOI: 10.1242/dmm.049463.

Synthetic regulatory reconstitution reveals principles of mammalian cluster regulation.

Pinglay S, Bulajic M, Rahe D, Huang E, Brosh R, Mamrak N Science. 2022; 377(6601):eabk2820.

PMID: 35771912 PMC: 9648154. DOI: 10.1126/science.abk2820.

Transcriptional silencing of fetal hemoglobin expression by NonO.

Li X, Chen M, Liu B, Lu P, Lv X, Zhao X Nucleic Acids Res. 2021; 49(17):9711-9723.

PMID: 34379783 PMC: 8464040. DOI: 10.1093/nar/gkab671.

Physiological and Aberrant γ-Globin Transcription During Development.

Barbarani G, Labedz A, Stucchi S, Abbiati A, Ronchi A Front Cell Dev Biol. 2021; 9:640060.

PMID: 33869190 PMC: 8047207. DOI: 10.3389/fcell.2021.640060.

A versatile platform for locus-scale genome rewriting and verification.

Brosh R, Laurent J, Ordonez R, Huang E, Hogan M, Hitchcock A Proc Natl Acad Sci U S A. 2021; 118(10).

PMID: 33649239 PMC: 7958457. DOI: 10.1073/pnas.2023952118.

References

HUISMAN T, Schroeder W, Efremov G, DUMA H, MLADENOVSKI B, Hyman C . The present status of the heterogeneity of fetal hemoglobin in beta-thalassemia: an attempt to unify some observations in thalassemia and related conditions. Ann N Y Acad Sci. 1974; 232(0):107-24. DOI: 10.1111/j.1749-6632.1974.tb20576.x. View

Palena A, Blau A, Stamatoyannopoulos G, Anagnou N . Eastern European (delta beta) zero-thalassemia: molecular characterization of a novel 9.1-kb deletion resulting in high levels of fetal hemoglobin in the adult. Blood. 1994; 83(12):3738-45. View

Gelinas R, Endlich B, Pfeiffer C, Yagi M, Stamatoyannopoulos G . G to A substitution in the distal CCAAT box of the A gamma-globin gene in Greek hereditary persistence of fetal haemoglobin. Nature. 1985; 313(6000):323-5. DOI: 10.1038/313323a0. View

Collins F, Metherall J, Yamakawa M, Pan J, Weissman S, Forget B . A point mutation in the A gamma-globin gene promoter in Greek hereditary persistence of fetal haemoglobin. Nature. 1985; 313(6000):325-6. DOI: 10.1038/313325a0. View

Choi O, Engel J . Developmental regulation of beta-globin gene switching. Cell. 1988; 55(1):17-26. DOI: 10.1016/0092-8674(88)90005-0. View

Feingold E, Forget B . The breakpoint of a large deletion causing hereditary persistence of fetal hemoglobin occurs within an erythroid DNA domain remote from the beta-globin gene cluster. Blood. 1989; 74(6):2178-86. View

Henthorn P, SMITHIES O, Mager D . Molecular analysis of deletions in the human beta-globin gene cluster: deletion junctions and locations of breakpoints. Genomics. 1990; 6(2):226-37. DOI: 10.1016/0888-7543(90)90561-8. View

Enver T, Raich N, Ebens A, Papayannopoulou T, Costantini F, Stamatoyannopoulos G . Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. Nature. 1990; 344(6264):309-13. DOI: 10.1038/344309a0. View

Behringer R, Ryan T, Palmiter R, Brinster R, Townes T . Human gamma- to beta-globin gene switching in transgenic mice. Genes Dev. 1990; 4(3):380-9. DOI: 10.1101/gad.4.3.380. View

10.

Raich N, Enver T, Nakamoto B, JOSEPHSON B, Papayannopoulou T, Stamatoyannopoulos G . Autonomous developmental control of human embryonic globin gene switching in transgenic mice. Science. 1990; 250(4984):1147-9. DOI: 10.1126/science.2251502. View

11.

Dillon N, Grosveld F . Human gamma-globin genes silenced independently of other genes in the beta-globin locus. Nature. 1991; 350(6315):252-4. DOI: 10.1038/350252a0. View

12.

Hanscombe O, Whyatt D, Fraser P, Yannoutsos N, Greaves D, Dillon N . Importance of globin gene order for correct developmental expression. Genes Dev. 1991; 5(8):1387-94. DOI: 10.1101/gad.5.8.1387. View

13.

Raich N, Papayannopoulou T, Stamatoyannopoulos G, Enver T . Demonstration of a human epsilon-globin gene silencer with studies in transgenic mice. Blood. 1992; 79(4):861-4. View

14.

Berry M, Grosveld F, Dillon N . A single point mutation is the cause of the Greek form of hereditary persistence of fetal haemoglobin. Nature. 1992; 358(6386):499-502. DOI: 10.1038/358499a0. View

15.

Strouboulis J, Dillon N, Grosveld F . Developmental regulation of a complete 70-kb human beta-globin locus in transgenic mice. Genes Dev. 1992; 6(10):1857-64. DOI: 10.1101/gad.6.10.1857. View

16.

Gnirke A, Huxley C, Peterson K, Olson M . Microinjection of intact 200- to 500-kb fragments of YAC DNA into mammalian cells. Genomics. 1993; 15(3):659-67. DOI: 10.1006/geno.1993.1121. View

17.

Peterson K, Stamatoyannopoulos G . Role of gene order in developmental control of human gamma- and beta-globin gene expression. Mol Cell Biol. 1993; 13(8):4836-43. PMC: 360110. DOI: 10.1128/mcb.13.8.4836-4843.1993. View

18.

Peterson K, Clegg C, Huxley C, JOSEPHSON B, Haugen H, Furukawa T . Transgenic mice containing a 248-kb yeast artificial chromosome carrying the human beta-globin locus display proper developmental control of human globin genes. Proc Natl Acad Sci U S A. 1993; 90(16):7593-7. PMC: 47188. DOI: 10.1073/pnas.90.16.7593. View

19.

Engel J . Developmental regulation of human beta-globin gene transcription: a switch of loyalties?. Trends Genet. 1993; 9(9):304-9. DOI: 10.1016/0168-9525(93)90248-g. View

20.

Stamatoyannopoulos G, JOSEPHSON B, Zhang J, Li Q . Developmental regulation of human gamma-globin genes in transgenic mice. Mol Cell Biol. 1993; 13(12):7636-44. PMC: 364835. DOI: 10.1128/mcb.13.12.7636-7644.1993. View