A transcriptomic analysis of human centromeric and pericentric sequences in normal and tumor cells.
Although there is now evidence that the expression of centromeric (CT) and pericentric (PCT) sequences are key players in major genomic functions, their transcriptional status in human cells is still poorly known. The main reason for this lack of data is the complexity and high level of polymorphism of these repeated sequences, which hampers straightforward analyses by available transcriptomic approaches. Here a transcriptomic macro-array dedicated to the analysis of CT and PCT expression is developed and validated in heat-shocked (HS) HeLa cells. For the first time, the expression status of CT and PCT sequences is analyzed in a series of normal and cancer human cells and tissues demonstrating that they are repressed in all normal tissues except in the testis, where PCT transcripts are found. Moreover, PCT sequences are specifically expressed in HS cells in a Heat-Shock Factor 1 (HSF1)-dependent fashion, and we show here that another independent pathway, involving DNA hypo-methylation, can also trigger their expression. Interestingly, CT and PCT were found illegitimately expressed in somatic cancer samples, whereas PCT were repressed in testis cancer, suggesting that the expression of CT and PCT sequences may represent a good indicator of epigenetic deregulations occurring in response to environmental changes or in cell transformation.
Eymery
Angéline
A
INSERM, U823, Université Joseph Fourier, Institut Albert Bonniot, La Tronche F-38706, Grenoble.
Horard
Béatrice
B
El Atifi-Borel
Michèle
M
Fourel
Geneviève
G
Berger
François
F
Vitte
Anne-Laure
AL
Van den Broeck
Arnaud
A
Brambilla
Elisabeth
E
Fournier
Alexandra
A
Callanan
Mary
M
Gazzeri
Sylvie
S
Khochbin
Saadi
S
Rousseaux
Sophie
S
Gilson
Eric
E
Vourc'h
Claire
C
D045744:Cell Line, Tumor; D002503:Centromere / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D020869:Gene Expression Profiling; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D043244:Ribonuclease III / Q000378:metabolism
D043244:Ribonuclease III