 |
|
|
 Patricia A. Wight
Professor
Ph.D, University of California, Riverside
Office: (501) 686-5366
Lab: (501) 686-5367
Email:
pwight@uams.edu
The
focus of research in my laboratory is centered on CNS development,
particularly with regard to the formation and maintenance of myelin. Myelin
is the tightly compacted multilamellar sheath, which surrounds axons and
promotes saltatory conduction of nerve impulses. The myelin proteolipid
protein (Plp) gene encodes the most abundant protein found in mature
myelin from the CNS. Expression of the gene is regulated spatiotemporally,
with maximal expression occurring in oligodendrocytes during the myelination
period of CNS development. Plp gene expression is tightly controlled;
misregulation of the gene in humans can result in the dysmyelinating
disorder Pelizaeus-Merzbacher disease, and in transgenic mice carrying a
null mutation or extra copies of the gene can result in a variety of
conditions, from late onset demyelination and axonopathy to severe early
onset dysmyelination. With the use of transgenic and transfection paradigms,
we have been able to show that the first intron of the Plp gene
contains a transcription regulatory element/region that controls temporal
expression in oligodendrocytes. We believe that this element acts as an
enhanceosome. In addition, the first intron also contains other regulatory
elements that act to modulate Plp gene activity in other cell types.
Current efforts in the laboratory are focused on identifying the
transcription factors/architectural proteins that bind to these regulatory
elements, and ultimately at elucidating the mechanisms whereby these
proteins affect Plp gene transcription.
Dr. Wight's Laboratory Homepage
Representative
Publications
Li S., Greuel B.T., Meng F., Pereira G.B., Pitts A.,
Dobretsova A., and Wight P.A. (2009) Leydig cells express the myelin
proteolipid protein gene and incorporate a new alternatively spliced
exon. Gene 436:30-36
Dobretsova A., Johnson J.W., Jones
R.C., Edmondson R.D., and Wight P.A. (2008) Proteomic analysis of
nuclear factors binding to an intronic enhancer in the myelin
proteolipid protein gene. J.
Neurochem. 105:1979-1995.
Wight P.A., Duchala
C.S., Gudz T.I., Shick H.E., and Macklin W.B. (2007) Expression of a
myelin proteolipid
protein (Plp)-lacZ
transgene is reduced in both the CNS and PNS of
Plpjp mice.
Neurochem. Res.
32:343-351.
Meng F.,
Zolova O.,
Kokorina N.A.,
Dobretsova A., and
Wight P.A. (2005)
Characterization of
an intronic enhancer that regulates myelin proteolipid protein (Plp)
gene expression in oligodendrocytes. J. Neurosci. Res. 82:346-356.
Dobretsova A.,
Kokorina N.A., and Wight P.A. (2004) Potentiation of myelin proteolipid
protein (Plp) gene expression is mediated through AP-1-like binding sites.
J. Neurochem. 90:1500-1510.
Wight P. A. and
Dobretsova A. (2004) Where, when and how much: regulation of myelin
proteolipid protein gene expression. Cell. Mol. Life Sci. 61:810-821.
Li S., Moore C.L.,
Dobretsova A., and Wight P.A. (2002). Myelin proteolipid protein (Plp)
intron 1 DNA is required to temporally regulate Plp gene expression in the
brain. J. Neurochem. 83:193-201.
Li S., Dobretsova
A., Kokorina N.A., and Wight P.A. (2002) Repression of myelin proteolipid
protein gene expression is mediated through both general and cell
type-specific negative regulatory elements in non-expressing cells. J.
Neurochem. 82:159-171.
Link
to Dr. Wight at Pub-Med
Questions about this page? Send us an email.
All contents © 2000-2006.
UAMS Online
Copyright
Statement
Privacy Statement
updated 12/20/06
|
|
