1: Ann Hum Genet. 2005 Sep;69(Pt 5):508-16. 

Evidence by expression analysis of candidate genes for congenital heart defects
in the NF1 microdeletion interval.

Venturin M, Bentivegna A, Moroni R, Larizza L, Riva P.

Department of Biology and Genetics, Medical Faculty--University of Milan, Italy.

It was recently reported that congenital heart disease is significantly more
frequent in patients with NF1 microdeletion syndrome than in those with
classical NF1. The outcome of congenital heart disease in this subset of
patients is likely caused by the haploinsufficiency of gene/s in the deletion
interval. Following in silico analysis of the deleted region, we found two genes
known to be expressed in adult heart, the Joined to JAZF1 (SUZ12) and the
Centaurin-alpha 2 (CENTA2) genes, and seven other genes with poorly defined
patterns of expression and function. With the aim of defining their expression
profiles in human fetal tissues (15th-21st weeks of gestation), expression
analysis by RT-PCR and Northern blotting was performed. C17orf40, SUZ12 and
CENTA2 were found to be mainly expressed in fetal heart, and following RT-PCR on
mouse embryos and embryonic heart and brain at different stages of development,
we found that the orthologous genes C17orf40, Suz12 and Centa2 are also
expressed in early stages of development, before and during the formation of the
four heart chambers. The presence of binding sites for Nkx2-5, a transcription
factor expressed early in heart development, in all three mouse orthologous
genes was predicted by bioinformatics, thus reinforcing the hypothesis that
these genes might be involved in heart development and may be plausible
candidates for congenital heart disease.

PMID: 16138909 [PubMed - in process]


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2: Gene. 2002 Jul 10;294(1-2):259-68. 

Structural and functional characterization of the human PAX7 5'-flanking
regulatory region.

Syagailo YV, Okladnova O, Reimer E, Grassle M, Mossner R, Gattenlohner S, Marx
A, Meyer J, Lesch KP.

Department of Psychiatry and Psychotherapy, University of Wurzburg,
Fuchsleinstrasse 15, 97080, Wurzburg, Germany.

The human PAX7 gene is a member of the paired box containing gene family of
transcription factors implicated in development of the skeletal muscle of the
trunk and limbs as well as elements of the central nervous system. To understand
the molecular mechanisms involved in its expression, we have localized the
transcription start sites in adult skeletal muscle and functionally
characterized the 5'-flanking regulatory region responsible for PAX7 expression
in this tissue. The major transcription start was identified 664 bp upstream
from the ATG codon using primer extension and 5'-rapid amplification of cDNA
ends (5'-RACE). Analysis of the 5'-flanking sequence revealed the absence of a
TATA-box and the presence of an inverted CCAAT-box. Several consensus sites for
common transcriptional regulators including Oct-1, NF1, AP2, AP4, CREB, Sp1,
Nkx2.5, and MyoD are present in the promoter region. To determine the sites
critical for the function of the PAX7 promoter, a series of deletion fragments
of the 5'-flanking region were cloned adjacent to luciferase reporter gene and
expressed in RD, Cos-7 and JAR cell lines. The maximal promoter activity was
achieved by a fragment extending from the position -403 to +373. No strong
positive or negative regulatory elements were discovered by adding of further
sequences (up to 2.97 kb). A polymorphic (CCT)(n) repeat sequence was found 107
bp upstream of the transcription initiation site. PCR-based systematic screening
for length variations in 227 unrelated individuals of a Caucasian population
showed a bimodal distribution of three alleles containing 8, 10 or 11 repeat
units. When different variants of this PAX7 gene-linked polymorphic region
(PAX7-LPR) were fused to a luciferase reporter gene and transfected into RD
cells, the variant with 11 repeat units revealed higher transcriptional
efficiency compared to the 8 or 10 repeat alleles.

PMID: 12234688 [PubMed - indexed for MEDLINE]


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