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The genetic mechanisms that regulate CFTR, the gene responsible for cystic fibrosis, have been widely investigated in cultured cells. However, mechanisms responsible for tissue-specific and time-specific expression are not completely elucidated in vivo. Through the survey of public databases, we found that the promoter of CFTRwas associated with bivalent chromatin in human embryonic stem (ES) cells. In this work, we analyzed fetal (at different stages of pregnancy) and adult tissues and showed that, in digestive and lung tissues, which expressed CFTR, H3K4me3 was maintained in the promoter. Histone acetylation was high in the promoter and in two intronic enhancers, especially in fetal tissues. In contrast, in blood cells, which did not express CFTR, the bivalent chromatin was resolved (the promoter was labeled by the silencing mark H3K27me3). Cis-regulatory sequences were associated with lowly acetylated histones. We also provide evidence that the tissue-specific expression of CFTRis not regulated by dynamic changes of DNA methylation in the promoter. Overall, this work shows that a balance between activating and repressive histone modifications in the promoter and intronic enhancers results in the fine regulation of CFTRexpression during development, thereby ensuring tissue specificity.

We have investigated the GC levels of third codon position of genes localized in G- (Giemsa), R- (reverse) and T- (telomeric) bands of human metaphase chromosomes, as well as the hybridization of telomeric probes on fractionated human DNA. The first set of results shows much higher GC levels for genes localized in T-bands than in G- or R-bands (the latter being higher than the former). The second set of data shows that telomeric probes corresponding to T-bands hybridize on the GC-richest family (H3) of isochores, whereas telomeric probes corresponding to R-bands hybridize on GC-rich families H1 and H2; in agreement with these findings, the telomeric repeat common to all chromosomes hybridized on isochore families H1, H2 and H3.

We have investigated the GC levels of third codon position of genes localized in G‐ (Giemsa), R‐ (reverse) and T‐ (telomeric) bands of human metaphase chromosomes, as well as the hybridization of telomeric probes on fractionated human DNA. The first set of results shows much higher GC levels for genes localized in T‐bands than in G‐ or R‐bands (the latter being higher than the former). The second set of data shows that telomeric probes corresponding to T‐bands hybridize on the GC‐richest family (H3) of isochores, whereas telomeric probes corresponding to R‐bands hybridize on GC‐rich families H1 and H2; in agreement with these findings, the telomeric repeat common to all chromosomes hybridized on isochore families H1, H2 and H3.

We report the isolation and characterization of a novel cDNA IGSF3 that contains a 3648-bp open reading frame encoding an apparent immunoglobulin (Ig)-like membrane protein characterized by eight Ig domains. IGSF3 has an overall structural similarity and strong sequence similarity to V7, a human leukocyte surface protein. The IGSF3 mRNA is highly expressed in placenta, kidney, and lung, but is also present in a wide range of other human tissues. Although a small internal sequence of the IGSF3 cDNA hybridizes to a YAC derived from the centromeric region of chromosome 21,in situhybridization experiments on human metaphase chromosomes show that the gene corresponding to the long cDNA that we cloned is located in chromosome band 1p13 and that related sequences are located on chromosomes 2 and 13. These data serve to emphasize the potential difficulties in transcriptional mapping in centromeric regions.