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PMID: 8248229 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Use of yeast artificial chromosomes (YACs) for studying control of gene expression: correct regulation of the genes of a human beta-globin locus YAC following transfer to mouse erythroleukemia cell lines.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 23 ·1993-12-01 ·Pages 11207-11

Peterson KR, Zitnik G, Huxley C, Lowrey CH, Gnirke A, Leppig KA, Papayannopoulou T, Stamatoyannopoulos G

Abstract

We demonstrate that transfer of a yeast artificial chromosome (YAC) containing 230 kb of the human beta-globin locus into mouse erythroleukemia cells by fusion results in correct developmental regulation of the human beta-like globin genes. Additionally, we show that early after hybrid formation, human embryonic epsilon- and fetal gamma-globin genes are coexpressed with the adult beta gene but that after 10-20 weeks in culture, globin gene expression switches to predominantly adult. Thus, in contrast to shorter gene constructs, the globin genes of the beta-globin locus YAC are regulated like the chromosomal globin genes. These results indicate that transfer of YACs into established cell lines can be used for the analysis of the developmental control of multigenic and developmentally regulated human loci.

MeSH Terms

Animals Chromosomes, Artificial, Yeast Gene Expression Regulation Gene Transfer Techniques Globins/genetics Humans Leukemia, Erythroblastic, Acute/genetics Mice RNA, Messenger/genetics Transcriptional Activation

Chemicals

RNA, Messenger Globins

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Peterson K R

Division of Medical Genetics, University of Washington, Seattle 98195.

Zitnik G

Huxley C

Lowrey C H

Gnirke A

Leppig K A

Papayannopoulou T

Stamatoyannopoulos G

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22 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.90.23.11207

Published

1993-12-01

Pages

11207-11

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC47951

Subset

Grants

NIDDK NIH HHS · DK30852 · United States

NIDDK NIH HHS · DK45365 · United States

NHLBI NIH HHS · HL20899 · United States

Corrections

ErratumIn

External Links

PubMed source DOI: 10.1073/pnas.90.23.11207 PMC Full Text View journal details

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Use of yeast artificial chromosomes (YACs) for studying control of gene expression: correct regulation of the genes of a human beta-globin locus YAC following transfer to mouse erythroleukemia cell lines.

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