Mechanism governing a stem cell-generating cis-regulatory element
Identifieur interne : 002843 ( Main/Exploration ); précédent : 002842; suivant : 002844Mechanism governing a stem cell-generating cis-regulatory element
Auteurs : Rajendran Sanalkumar ; Kirby D. Johnson ; Xin Gao ; Meghan E. Boyer ; Yuan-I Chang ; Kyle J. Hewitt ; Jing Zhang ; Emery H. BresnickSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Abstract
The continuous replenishment of differentiated cells, for example, those constituting the blood, involves proteins that control the generation and function of stem and progenitor cells. Although “master regulators” are implicated in these processes, many questions remain unanswered regarding how their synthesis and activities are regulated. We describe a mechanism that controls the production of the master regulator GATA binding protein-2 (GATA-2) in the context of blood stem and progenitor cells. Thousands of GATA-2 binding sites exist in the genome, and genetic analyses indicate that they differ greatly and unpredictably in functional importance. The parameters involved in endowing sites with functional activity are not established. We describe unique insights into ascertaining functionally important GATA-2 binding sites within chromosomes.
Url:
DOI: 10.1073/pnas.1400065111
PubMed: 24616499
PubMed Central: 3970491
Affiliations:
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Johnson</name><affiliation><nlm:aff id="aff1">Department of Cell and Regenerative Biology, Wisconsin Institutes for Medical Research, Carbone Cancer Center,<institution>University of Wisconsin School of Medicine and Public Health</institution>, Madison,<addr-line>WI</addr-line> 53705;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>University of Wisconsin–Madison Blood Research Program</institution>, Madison,<addr-line>WI</addr-line> 53705</nlm:aff></affiliation></author><author><name sortKey="Gao, Xin" sort="Gao, Xin" uniqKey="Gao X" first="Xin" last="Gao">Xin Gao</name><affiliation><nlm:aff id="aff1">Department of Cell and Regenerative Biology, Wisconsin Institutes for Medical Research, Carbone Cancer Center,<institution>University of Wisconsin School of Medicine and Public Health</institution>, Madison,<addr-line>WI</addr-line> 53705;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>University of Wisconsin–Madison Blood Research Program</institution>, Madison,<addr-line>WI</addr-line> 53705</nlm:aff></affiliation></author><author><name sortKey="Boyer, Meghan E" sort="Boyer, Meghan E" uniqKey="Boyer M" first="Meghan E." last="Boyer">Meghan E. Boyer</name><affiliation><nlm:aff id="aff1">Department of Cell and Regenerative Biology, Wisconsin Institutes for Medical Research, Carbone Cancer Center,<institution>University of Wisconsin School of Medicine and Public Health</institution>, Madison,<addr-line>WI</addr-line> 53705;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>University of Wisconsin–Madison Blood Research Program</institution>, Madison,<addr-line>WI</addr-line> 53705</nlm:aff></affiliation></author><author><name sortKey="Chang, Yuan I" sort="Chang, Yuan I" uniqKey="Chang Y" first="Yuan-I" last="Chang">Yuan-I Chang</name><affiliation><nlm:aff id="aff3"><institution>University of Wisconsin–Madison Blood Research Program</institution>, Madison,<addr-line>WI</addr-line> 53705</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff2">McArdle Laboratory for Cancer Research,<institution>University of Wisconsin School of Medicine and Public Health</institution>, Madison,<addr-line>WI</addr-line> 53706</nlm:aff></affiliation></author><author><name sortKey="Hewitt, Kyle J" sort="Hewitt, Kyle J" uniqKey="Hewitt K" first="Kyle J." last="Hewitt">Kyle J. Hewitt</name><affiliation><nlm:aff id="aff1">Department of Cell and Regenerative Biology, Wisconsin Institutes for Medical Research, Carbone Cancer Center,<institution>University of Wisconsin School of Medicine and Public Health</institution>, Madison,<addr-line>WI</addr-line> 53705;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>University of Wisconsin–Madison Blood Research Program</institution>, Madison,<addr-line>WI</addr-line> 53705</nlm:aff></affiliation></author><author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name><affiliation><nlm:aff id="aff3"><institution>University of Wisconsin–Madison Blood Research Program</institution>, Madison,<addr-line>WI</addr-line> 53705</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff2">McArdle Laboratory for Cancer Research,<institution>University of Wisconsin School of Medicine and Public Health</institution>, Madison,<addr-line>WI</addr-line> 53706</nlm:aff></affiliation></author><author><name sortKey="Bresnick, Emery H" sort="Bresnick, Emery H" uniqKey="Bresnick E" first="Emery H." last="Bresnick">Emery H. Bresnick</name><affiliation><nlm:aff id="aff1">Department of Cell and Regenerative Biology, Wisconsin Institutes for Medical Research, Carbone Cancer Center,<institution>University of Wisconsin School of Medicine and Public Health</institution>, Madison,<addr-line>WI</addr-line> 53705;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>University of Wisconsin–Madison Blood Research Program</institution>, Madison,<addr-line>WI</addr-line> 53705</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>The continuous replenishment of differentiated cells, for example, those constituting the blood, involves proteins that control the generation and function of stem and progenitor cells. Although “master regulators” are implicated in these processes, many questions remain unanswered regarding how their synthesis and activities are regulated. We describe a mechanism that controls the production of the master regulator GATA binding protein-2 (GATA-2) in the context of blood stem and progenitor cells. Thousands of GATA-2 binding sites exist in the genome, and genetic analyses indicate that they differ greatly and unpredictably in functional importance. The parameters involved in endowing sites with functional activity are not established. We describe unique insights into ascertaining functionally important GATA-2 binding sites within chromosomes.</p></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Boyer, Meghan E" sort="Boyer, Meghan E" uniqKey="Boyer M" first="Meghan E." last="Boyer">Meghan E. Boyer</name><name sortKey="Bresnick, Emery H" sort="Bresnick, Emery H" uniqKey="Bresnick E" first="Emery H." last="Bresnick">Emery H. Bresnick</name><name sortKey="Chang, Yuan I" sort="Chang, Yuan I" uniqKey="Chang Y" first="Yuan-I" last="Chang">Yuan-I Chang</name><name sortKey="Gao, Xin" sort="Gao, Xin" uniqKey="Gao X" first="Xin" last="Gao">Xin Gao</name><name sortKey="Hewitt, Kyle J" sort="Hewitt, Kyle J" uniqKey="Hewitt K" first="Kyle J." last="Hewitt">Kyle J. Hewitt</name><name sortKey="Johnson, Kirby D" sort="Johnson, Kirby D" uniqKey="Johnson K" first="Kirby D." last="Johnson">Kirby D. Johnson</name><name sortKey="Sanalkumar, Rajendran" sort="Sanalkumar, Rajendran" uniqKey="Sanalkumar R" first="Rajendran" last="Sanalkumar">Rajendran Sanalkumar</name><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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