Relationship between replication and transcriptional activity within the type 1 keratin gene cluster

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133814

Belanger, C; Royal, A; Lemieux, N ^[1]

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1. Univerite de Montreal, Quebec (Canada)

Tissue-specific genes are usually replicated according to a developmentally regulated pattern: early in cells expressing those particular genes and late in non-expressing cell types. To study the relationship between transcriptional activity and replication time in relation to cell differentiation, the type 1 keratin gene cluster (Krt-1) was chosen as a model. This relationship is very complex, particularly in multigene families, because genes are not expressed at the same time during development or cellular differentiation. To determine if the Krt-1 cluster behaves as a single functional unit or is subdivided into functionally distinct regions, we have defined the replication times of two specific sequences within the locus with different patterns of expression. The analyses were performed by FISH techniques on mouse non-synchronous interphase nuclei obtained from different cell lines: KLN 205 and OBL 24. The results show two distinct units: a region containing three type 1 keratin genes, K19, K15 and K13, which seem to behave as a single functional unit and a region containing the K10 gene. We have obtained a high percentage of double signals with K19, K15, and K13 genes whereas most nuclei showed single hybridization dots with the K10 gene. Furthermore, the K19, K15, K13 region seems to replicate earlier than the K10 gene in KLN 205 cells. In contrast, no relation between replication time and epithelial differentiation type was found with two reference probes: the hypoxanthine phosphorybosyl transferase gene (HPRT), early replicating in all the cells examined, and the peripherin gene which is expected to be late replicating in epithelial cells. Comparison of the replication times of sequences used within the Krt-1 locus suggests that this locus behaves as at least two distinct domains related to different type 1 keratin gene expression in distinct tissues.

• OSTI ID: 133814
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MODELS
CELL DIFFERENTIATION
CELL NUCLEI
DNA HYBRIDIZATION
DNA REPLICATION
DNA SEQUENCING
FLUORESCENCE
GENE REGULATION
GENES
KERATIN
MICE
STRUCTURE-ACTIVITY RELATIONSHIPS
TISSUE DISTRIBUTION
TRANSCRIPTION