Regulation of activity of the transcription factor GATA-1 by acetylation
Modification of histones, DNA-binding proteins found in chromatin, by addition of acetyl groups occurs to a greater degree when the histones are associated with transcriptionally active DNA 1 , 2 . A breakthrough in understanding how this acetylation is mediated was the discovery that various transc...
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Veröffentlicht in: | Nature (London) 1998-12, Vol.396 (6711), p.594-598 |
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description | Modification of histones, DNA-binding proteins found in chromatin, by addition of acetyl groups occurs to a greater degree when the histones are associated with transcriptionally active DNA
1
,
2
. A breakthrough in understanding how this acetylation is mediated was the discovery that various transcriptional co-activator proteins have intrinsic histone acetyltransferase activity (for example, Gcn5p (
ref. 3
), PCAF
4
, TAF
II
250 (
ref. 5
) and p300/CBP
6
,
7
). These acetyltransferases also modify certain transcription factors (TFIIEβ, TFIIF, EKLF and p53 (
8
–
10
)). GATA-1 is an important transcription factor in the haematopoietic lineage
11
and is essential for terminal differentiation of erythrocytes and megakaryocytes
12
,
13
. It is associated
in vivo
with the acetyltransferase p300/CBP
14
. Here we report that GATA-1 is acetylated
in vitro
by p300. This significantly increases the amount of GATA-1 bound to DNA and alters the mobility of GATA-1–DNA complexes, suggestive of a conformational change in GATA-1. GATA-1 is also acetylated
in vivo
and acetylation directly stimulates GATA-1-dependent transcription. Mutagenesis of important acetylated residues shows that there is a relationship between the acetylation and
in vivo
function of GATA-1. Wepropose that acetylation of transcription factors can alter interactions between these factors and DNA and among different transcription factors, and is an integral part of transcription and differentiation processes. |
doi_str_mv | 10.1038/25166 |
format | Article |
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1
,
2
. A breakthrough in understanding how this acetylation is mediated was the discovery that various transcriptional co-activator proteins have intrinsic histone acetyltransferase activity (for example, Gcn5p (
ref. 3
), PCAF
4
, TAF
II
250 (
ref. 5
) and p300/CBP
6
,
7
). These acetyltransferases also modify certain transcription factors (TFIIEβ, TFIIF, EKLF and p53 (
8
–
10
)). GATA-1 is an important transcription factor in the haematopoietic lineage
11
and is essential for terminal differentiation of erythrocytes and megakaryocytes
12
,
13
. It is associated
in vivo
with the acetyltransferase p300/CBP
14
. Here we report that GATA-1 is acetylated
in vitro
by p300. This significantly increases the amount of GATA-1 bound to DNA and alters the mobility of GATA-1–DNA complexes, suggestive of a conformational change in GATA-1. GATA-1 is also acetylated
in vivo
and acetylation directly stimulates GATA-1-dependent transcription. Mutagenesis of important acetylated residues shows that there is a relationship between the acetylation and
in vivo
function of GATA-1. Wepropose that acetylation of transcription factors can alter interactions between these factors and DNA and among different transcription factors, and is an integral part of transcription and differentiation processes.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/25166</identifier><identifier>PMID: 9859997</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>3T3 Cells ; Acetylation ; Amino Acid Sequence ; Animals ; Binding Sites ; Biological and medical sciences ; Cellular biology ; Chickens ; Deoxyribonucleic acid ; DNA ; DNA - metabolism ; DNA-Binding Proteins - metabolism ; E1A-Associated p300 Protein ; Erythroid-Specific DNA-Binding Factors ; Fundamental and applied biological sciences. Psychology ; GATA1 Transcription Factor ; Humanities and Social Sciences ; letter ; Lysine - metabolism ; Mass Spectrometry ; Mice ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; multidisciplinary ; Nuclear Proteins - metabolism ; Protein Binding ; Proteins ; Science ; Science (multidisciplinary) ; Trans-Activators - metabolism ; Transcription Factors - metabolism ; Transcription, Genetic ; Transcription. Transcription factor. Splicing. Rna processing ; Tumor Cells, Cultured ; Zinc Fingers</subject><ispartof>Nature (London), 1998-12, Vol.396 (6711), p.594-598</ispartof><rights>Macmillan Magazines Ltd. 1998</rights><rights>1999 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. Dec 10, 1998</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-e388cf02af60cc968d3fb2285a297f6793e52c5c609e725342dabc5e77db723f3</citedby><cites>FETCH-LOGICAL-c552t-e388cf02af60cc968d3fb2285a297f6793e52c5c609e725342dabc5e77db723f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/25166$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/25166$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1642766$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9859997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boyes, Joan</creatorcontrib><creatorcontrib>Byfield, Peter</creatorcontrib><creatorcontrib>Nakatani, Yoshihiro</creatorcontrib><creatorcontrib>Ogryzko, Vasily</creatorcontrib><title>Regulation of activity of the transcription factor GATA-1 by acetylation</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Modification of histones, DNA-binding proteins found in chromatin, by addition of acetyl groups occurs to a greater degree when the histones are associated with transcriptionally active DNA
1
,
2
. A breakthrough in understanding how this acetylation is mediated was the discovery that various transcriptional co-activator proteins have intrinsic histone acetyltransferase activity (for example, Gcn5p (
ref. 3
), PCAF
4
, TAF
II
250 (
ref. 5
) and p300/CBP
6
,
7
). These acetyltransferases also modify certain transcription factors (TFIIEβ, TFIIF, EKLF and p53 (
8
–
10
)). GATA-1 is an important transcription factor in the haematopoietic lineage
11
and is essential for terminal differentiation of erythrocytes and megakaryocytes
12
,
13
. It is associated
in vivo
with the acetyltransferase p300/CBP
14
. Here we report that GATA-1 is acetylated
in vitro
by p300. This significantly increases the amount of GATA-1 bound to DNA and alters the mobility of GATA-1–DNA complexes, suggestive of a conformational change in GATA-1. GATA-1 is also acetylated
in vivo
and acetylation directly stimulates GATA-1-dependent transcription. Mutagenesis of important acetylated residues shows that there is a relationship between the acetylation and
in vivo
function of GATA-1. Wepropose that acetylation of transcription factors can alter interactions between these factors and DNA and among different transcription factors, and is an integral part of transcription and differentiation processes.</description><subject>3T3 Cells</subject><subject>Acetylation</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cellular biology</subject><subject>Chickens</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>E1A-Associated p300 Protein</subject><subject>Erythroid-Specific DNA-Binding Factors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>GATA1 Transcription Factor</subject><subject>Humanities and Social Sciences</subject><subject>letter</subject><subject>Lysine - metabolism</subject><subject>Mass Spectrometry</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>multidisciplinary</subject><subject>Nuclear Proteins - metabolism</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcription. Transcription factor. Splicing. 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Psychology</topic><topic>GATA1 Transcription Factor</topic><topic>Humanities and Social Sciences</topic><topic>letter</topic><topic>Lysine - metabolism</topic><topic>Mass Spectrometry</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>multidisciplinary</topic><topic>Nuclear Proteins - metabolism</topic><topic>Protein Binding</topic><topic>Proteins</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transcription. Transcription factor. Splicing. 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1
,
2
. A breakthrough in understanding how this acetylation is mediated was the discovery that various transcriptional co-activator proteins have intrinsic histone acetyltransferase activity (for example, Gcn5p (
ref. 3
), PCAF
4
, TAF
II
250 (
ref. 5
) and p300/CBP
6
,
7
). These acetyltransferases also modify certain transcription factors (TFIIEβ, TFIIF, EKLF and p53 (
8
–
10
)). GATA-1 is an important transcription factor in the haematopoietic lineage
11
and is essential for terminal differentiation of erythrocytes and megakaryocytes
12
,
13
. It is associated
in vivo
with the acetyltransferase p300/CBP
14
. Here we report that GATA-1 is acetylated
in vitro
by p300. This significantly increases the amount of GATA-1 bound to DNA and alters the mobility of GATA-1–DNA complexes, suggestive of a conformational change in GATA-1. GATA-1 is also acetylated
in vivo
and acetylation directly stimulates GATA-1-dependent transcription. Mutagenesis of important acetylated residues shows that there is a relationship between the acetylation and
in vivo
function of GATA-1. Wepropose that acetylation of transcription factors can alter interactions between these factors and DNA and among different transcription factors, and is an integral part of transcription and differentiation processes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>9859997</pmid><doi>10.1038/25166</doi><tpages>5</tpages></addata></record> |
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subjects | 3T3 Cells Acetylation Amino Acid Sequence Animals Binding Sites Biological and medical sciences Cellular biology Chickens Deoxyribonucleic acid DNA DNA - metabolism DNA-Binding Proteins - metabolism E1A-Associated p300 Protein Erythroid-Specific DNA-Binding Factors Fundamental and applied biological sciences. Psychology GATA1 Transcription Factor Humanities and Social Sciences letter Lysine - metabolism Mass Spectrometry Mice Molecular and cellular biology Molecular genetics Molecular Sequence Data multidisciplinary Nuclear Proteins - metabolism Protein Binding Proteins Science Science (multidisciplinary) Trans-Activators - metabolism Transcription Factors - metabolism Transcription, Genetic Transcription. Transcription factor. Splicing. Rna processing Tumor Cells, Cultured Zinc Fingers |
title | Regulation of activity of the transcription factor GATA-1 by acetylation |
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