PMID- 10654609
OWN - NLM
STAT- MEDLINE
DCOM- 20000303
LR  - 20171116
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 127
IP  - 1
DP  - 2000 Jan
TI  - Segmental expression of Hoxb2 in r4 requires two separate sites that integrate
      cooperative interactions between Prep1, Pbx and Hox proteins.
PG  - 155-66
AB  - Direct auto- and cross-regulatory interactions between Hox genes serve to
      establish and maintain segmentally restricted patterns in the developing
      hindbrain. Rhombomere r4-specific expression of both Hoxb1 and Hoxb2 depends upon
      bipartite cis Hox response elements for the group 1 paralogous proteins, Hoxal
      and Hoxbl. The DNA-binding ability and selectivity of these proteins depend upon 
      the formation of specific heterodimeric complexes with members of the PBC
      homeodomain protein family (Pbx genes). The r4 enhancers from Hoxb1 and Hoxb2
      have the same activity, but differ with respect to the number and organisation of
      bipartite Pbx/Hox (PH) sites required, suggesting the intervention of other
      components/sequences. We report here that another family of homeodomain proteins 
      (TALE, Three-Amino acids-Loop-Extension: Prep1, Meis, HTH), capable of dimerizing
      with Pbx/EXD, is involved in the mechanisms of r4-restricted expression. We show 
      that: (1) the r4-specific Hoxb1 and Hoxb2 enhancers are complex elements
      containing separate PH and Prep/Meis (PM) sites; (2) the PM site of the Hoxb2,
      but not Hoxb1, enhancer is essential in vivo for r4 expression and also
      influences other sites of expression; (3) both PM and PH sites are required for
      in vitro binding of Prepl-Pbx and formation and binding of a ternary Hoxbl-Pbxla 
      (or 1b)-Prepl complex. (4) A similar ternary association forms in nuclear
      extracts from embryonal P19 cells, but only upon retinoic acid induction. This
      requires synthesis of Hoxbl and also contains Pbx with either Prepl or Meisl.
      Together these findings highlight the fact that PM sites are found in close
      proximity to bipartite PH motifs in several Hox responsive elements shown to be
      important in vivo and that such sites play an essential role in potentiating
      regulatory activity in combination with the PH motifs.
FAU - Ferretti, E
AU  - Ferretti E
AD  - Molecular Genetics Unit, DIBIT, Universita Vita-Salute S. Raffaele, Milan, Italy.
FAU - Marshall, H
AU  - Marshall H
FAU - Popperl, H
AU  - Popperl H
FAU - Maconochie, M
AU  - Maconochie M
FAU - Krumlauf, R
AU  - Krumlauf R
FAU - Blasi, F
AU  - Blasi F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Cell Extracts)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HOXB1 homeodomain protein)
RN  - 0 (HOXB2 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxb2 protein, mouse)
RN  - 0 (PKNOX1 protein, human)
RN  - 0 (Pknox1 protein, mouse)
RN  - 0 (Pre-B-Cell Leukemia Transcription Factor 1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (pbx1 protein, human)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Body Patterning/*physiology
MH  - Cell Extracts
MH  - Cell Nucleus
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - *Gene Expression Regulation, Developmental
MH  - Homeodomain Proteins/*genetics/*metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Pre-B-Cell Leukemia Transcription Factor 1
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Rhombencephalon/*embryology
MH  - Transcription Factors/*genetics
MH  - Tretinoin/metabolism
EDAT- 2000/02/02 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/02 09:00
PHST- 2000/02/02 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/02 09:00 [entrez]
PST - ppublish
SO  - Development. 2000 Jan;127(1):155-66.