X-Message-Number: 30900
Date: Wed, 30 Jul 2008 10:18:48 -0700 (PDT)
From: 
Subject: prevailing theory of aging challenged

[They are implying that increased expression of elt-5 and elt-6 are prime
drivers of nematode aging. Curiously elt-5 and elt-6 also promote cell
differentiation.]

Cell, Vol 134, 291-303, 25 July 2008

Article
An elt-3/elt-5/elt-6 GATA Transcription Circuit Guides Aging in C. elegans

Yelena V. Budovskaya,1 Kendall Wu,1,3 Lucinda K. Southworth,2 Min Jiang,1 
Patricia Tedesco,4 Thomas E. Johnson,4 and Stuart K. Kim1,2,


1 Department of Developmental Biology, Stanford University Medical Center, 
Stanford, CA 94305, USA

2 Stanford Medical Informatics, Stanford University Medical Center, Stanford, CA
94305, USA
3 Affymetrix, Inc., 3420 Central Expressway, Santa Clara, CA 95051, USA

4 Institute for Behavioral Genetics, Department of Integrative Physiology, 
University of Colorado, Boulder, Box 447, Boulder, CO 80309, USA

Corresponding author
Stuart K. Kim

Summary


To define the C. elegans aging process at the molecular level, we used DNA 
microarray experiments to identify a set of 1294 age-regulated genes and found 
that the GATA transcription factors ELT-3, ELT-5, and ELT-6 are responsible for 
age regulation of a large fraction of these genes. Expression of

elt-5 and elt-6 increases during normal aging, and both of these GATA factors 
repress expression of elt-3, which shows a corresponding decrease in expression 
in old worms. elt-3 regulates a large number of downstream genes that change 
expression in old age, including ugt-9, col-144, and sod-3.

elt-5(RNAi) and elt-6(RNAi) worms have extended longevity, indicating that 
elt-3, elt-5, and elt-6 play an important functional role in the aging process. 
These results identify a transcriptional circuit that guides the rapid aging 
process in C. elegans and indicate that this circuit is driven by
drift of developmental pathways rather than accumulation of damage.

Development. 2001 Aug;128(15):2867-80.

ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell 
differentiation and cell fusion in C. elegans.

    Koh K, Rothman JH. Department of Molecular, Cellular, and Developmental 
    Biology and Neuroscience Research Institute, University of California, Santa
    Barbara, CA 93106, USA.

    The C. elegans epidermis is a simple epithelium comprised of three major 
    cell types, the seam, syncytial and P cells. While specification of all 
    major epidermal cells is known to require the ELT-1 GATA transcription 
    factor, little is known about how the individual epidermal cell types are

specified. We report that elt-5 and -6, adjacent genes encoding GATA factors, 
are essential for the development of the lateral epidermal cells, the seam 
cells. Inhibition of elt-5 and -6 function by RNA-mediated interference results 
in penetrant late embryonic and early larval lethality. Seam cells

in affected animals do not differentiate properly: the alae, seam-specific 
cuticular structures, are generally absent and expression of several 
seam-specific markers is blocked. In addition, elt-3, which encodes another GATA
factor normally expressed in non-seam epidermis, is often ectopically

expressed in the seam cells of affected animals, demonstrating that ELT-5 and -6
repress elt-3 expression in wild-type seam cells. Seam cells in affected 
animals often undergo inappropriate fusion with the epidermal syncytia. 
Interference of elt-5 and -6 function during larval development can cause

fusion of all seam cells with the surrounding syncytia and pronounced defects in
molting. elt-5 and -6 are both expressed in seam cells and many other cells, 
and are apparently functionally interchangeable. Their expression is controlled 
by separable tissue-specific regulatory elements and the

apportionment of monocistronic versus dicistronic transcription of both genes 
appears to be subject to cell-type-specific regulation. Collectively, these 
findings indicate that elt-5 and -6 function continuously throughout C. elegans 
development to regulate seam cell differentiation and cell fusion.
PMID: 11532911

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