Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P20226 (
TATA-binding protein
)
1,297
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
RET
gene is crucial for the development of enteric nervous system, and dys-regulation of
RET
expression causes Hirschsprung disease. HOXB5 regulates
RET
transcription, and perturbations in transcriptional regulation by HOXB5 caused reduced
RET
expression and defective enteric nervous system development in mice. The mechanisms by which HOXB5 regulate
RET
transcription are unclear. Thus, unraveling the regulatory mechanisms of HOXB5 on
RET
transcription could lead to a better understanding of the etiology of Hirschsprung disease. In this study, we identified and confirmed HOXB5 binding to the multi-species conserved sequence (MCS+9.7) in the first intron of the
RET
gene. We developed a
RET
mini-gene reporter system, and showed that MCS+9.7 enhanced HOXB5 trans-activation from
RET
promoter in human neuroblastoma SK-N-SH cells and in chick embryos. The deletion of HOXB5 binding site interfered with HOXB5 trans-activation. Furthermore, transfection of HOXB5 induced endogenous
RET
transcription, enhanced the co-precipitation of
TATA-box binding protein
with the transcription start site of
RET
, and induced histone H3K4 trimethylation in chromatin regions upstream and downstream of
RET
transcription start site. In conclusion, (i) HOXB5 physically interacted with MCS+9.7 and enhanced
RET
transcription, (ii) HOXB5 altered chromatin conformation and histone modification of
RET
locus, which could facilitate the formation of transcription complex, and enhance
RET
transcription, (iii) expression of
RET
was mediated by a complex regulatory network of transcription factors functioning in a synergistic, additive and/or independent manners. Hence, dys-regulation of
RET
expression by HOXB5 could result in insufficient
RET
expression and Hirschsprung disease.
...
PMID:HOXB5 binds to multi-species conserved sequence (MCS+9.7) of RET gene and regulates RET expression. 2479 74
