INVESTIGADORES
SILVA JUNQUEIRA DE SOUZA Flavio
congresos y reuniones científicas
Título:
Uncovering cis- and trans-acting code regulating proopimelanocortin transcription in the brain
Autor/es:
NASIF S; DE SOUZA FS; LÓPEZ LEAL RA; RUBINSTEIN M
Reunión:
Congreso; XLV Reunión anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009
Resumen:
The proopiomelanocortin gene (POMC) encodes a prohormone that is
expressed mainly in the pituitary and the arcuate nucleus of the
hypothalamus, playing a central role in the stress response and energy
balance, respectively. We have showed that hypothalamic expression of
POMC is driven by two upstream enhancers, nPE1 and nPE2. To identify the
critical secuences of nPE1 (630 bp) we performed a bioinformatic
analysis coupled with an expression study in transgenic mice. Using this
strategy we unraveled a functionally critical 144 bp central region
within nPE1 that is necessary and sufficient to drive reporter gene
expression to POMC neurons in transgenic mice. Comparison of this
critical nPE1 region with those previously identified in nPE2 evidenced a
number of short conserved sequences that are present in both enhancers,
suggesting that the transcriptional activity of nPE1 and nPE2 might be
conferred by a similar set of homeodomain containing transcription
factors (HDTF). Data from the literature and from a UNIPROBE search led
us to test the ability of several recombinant HDTF candidates to bind to
the enhancers regions in gel shift assays. Our results represent a
step forward to elucidate the transcriptional code of POMC in the brain
and the understanding of the overlapping functions of nPE1 and nPE2.