PMID- 10206974
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 17
DP  - 1999 Apr 23
TI  - Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-binding site.
PG  - 11635-42
AB  - The recently described Hmx family of homeodomain proteins is predominately
      expressed in discrete regions of developing sensory tissues. In this report, we
      have identified the preferred DNA-binding site of the murine Hmx3 homeodomain
      protein by the selection and amplification binding (SAAB) technique. The
      consensus Hmx-binding site contained the sequence 5'-CAAGTG-3', which differs
      from the 5'-TAAT-3' motif commonly associated with homeodomain proteins. Instead,
      the Hmx consensus is similar to the 5'-CAAGTG-3'-binding sites of Nkx2.1 and
      Nkx2.5 homeodomain proteins. Based on mutation studies, both the 5'-CAAG-3' core 
      and the 3'-TG dinucleotide are required for high affinity binding by Hmx3 and the
      homologous Hmx1 protein. A critical determinant of this specificity is the
      glutamine at position 50 in the third helix of the Hmx homeodomain. Hmx1 binds to
      the 5'-CAAGTG-3' element with an apparent dissociation constant of 20 nM.
      Unexpectedly, the human Hmx1 protein specifically repressed transcription from a 
      luciferase reporter gene containing 3 copies of the 5'-CAAGTG-3' sequence. In
      contrast, the Nkx2.5 protein transactivated this luciferase reporter.
      Interestingly, co-expression of Hmx1 and Nkx2.5 attenuated each others activity, 
      suggesting that genes containing the CAAGTG element can integrate signals from
      these proteins. Therefore, Hmx1 and Nkx2. 5 proteins bind a unique DNA sequence
      and act as transcriptional antagonists.
FAU - Amendt, B A
AU  - Amendt BA
AD  - Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa
      52242, USA. brad-amendt@uiowa.edu
FAU - Sutherland, L B
AU  - Sutherland LB
FAU - Russo, A F
AU  - Russo AF
LA  - eng
GR  - DE09170/DE/NIDCR NIH HHS/United States
GR  - DK25295/DK/NIDDK NIH HHS/United States
GR  - HD25969/HD/NICHD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeobox Protein Nkx-2.5)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NKX2-5 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Xenopus Proteins)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites
MH  - DNA Primers
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Homeobox Protein Nkx-2.5
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Mutation
MH  - *Transcription Factors
MH  - *Transcription, Genetic
MH  - *Xenopus Proteins
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 - 10.1074/jbc.274.17.11635 [doi]
AID - S0021-9258(19)73475-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 23;274(17):11635-42. doi: 10.1074/jbc.274.17.11635.