PMID- 10207073
OWN - NLM
STAT- MEDLINE
DCOM- 19990518
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 5
DP  - 1999 May
TI  - CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at
      functionally important sites.
PG  - 3496-505
AB  - The transcription factor GATA-1 is a key regulator of erythroid-cell
      differentiation and survival. We have previously shown that the transcriptional
      cofactor CREB-binding protein (CBP) binds to the zinc finger domain of GATA-1,
      markedly stimulates the transcriptional activity of GATA-1, and is required for
      erythroid differentiation. Here we report that CBP, but not p/CAF, acetylates
      GATA-1 at two highly conserved lysine-rich motifs present at the C-terminal tails
      of both zinc fingers. Using [3H]acetate labelling experiments and anti-acetyl
      lysine immunoprecipitations, we show that GATA-1 is acetylated in vivo at the
      same sites acetylated by CBP in vitro. In addition, we show that CBP stimulates
      GATA-1 acetylation in vivo in an E1A-sensitive manner, thus establishing a
      correlation between acetylation and transcriptional activity of GATA-1.
      Acetylation in vitro did not alter the ability of GATA-1 to bind DNA, and
      mutations in either motif did not affect DNA binding of GATA-1 expressed in
      mammalian cells. Since certain functions of GATA-1 are revealed only in an
      erythroid environment, GATA-1 constructs were examined for their ability to
      trigger terminal differentiation when introduced into a GATA-1-deficient
      erythroid cell line. We found that mutations in either acetylation motif
      partially impaired the ability of GATA-1 to induce differentiation while
      mutations in both motifs abrogated it completely. Taken together, these data
      indicate that CBP is an important cofactor for GATA-1 and suggest a novel
      mechanism in which acetylation by CBP regulates GATA-1 activity in erythroid
      cells.
FAU - Hung, H L
AU  - Hung HL
AD  - Division of Hematology, Children's Hospital of Philadelphia, Philadelphia,
      Pennsylvania 19104, USA.
FAU - Lau, J
AU  - Lau J
FAU - Kim, A Y
AU  - Kim AY
FAU - Weiss, M J
AU  - Weiss MJ
FAU - Blobel, G A
AU  - Blobel GA
LA  - eng
GR  - P30 CA016520/CA/NCI NIH HHS/United States
GR  - P30 DK019525/DK/NIDDK NIH HHS/United States
GR  - CA-16520/CA/NCI NIH HHS/United States
GR  - DK-19525/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Adenovirus E1A Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Erythroid-Specific DNA-Binding Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Acetylation
MH  - Adenovirus E1A Proteins/metabolism
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - CREB-Binding Protein
MH  - Cell Differentiation
MH  - Cell Line
MH  - Conserved Sequence/genetics
MH  - DNA-Binding Proteins/*metabolism
MH  - Erythroid-Specific DNA-Binding Factors
MH  - Lysine/genetics/metabolism
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - Nuclear Proteins/*metabolism
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - Transfection
MH  - Zinc Fingers/genetics
PMC - PMC84142
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - 10.1128/MCB.19.5.3496 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 May;19(5):3496-505. doi: 10.1128/MCB.19.5.3496.