Active alleles of the human XIST gene replicate late in S phase

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

OSTI ID:133383

Hansen, R S; Gartler, S M ^[1]

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1. Univ. of Washington, Seattle, WA (United States)

The XIST gene is a strong candidate for controlling X chromosome inactivation. It has been mapped to the X inactivation control region (Xic) and is transcribed exclusively from the inactive X chromosome. XIST expression during development appears to be controlled by epigenetic modulation. Replication timing is an epigenetic modification implicated in transcriptional control and chromosomal imprinting. We have studied the replication timing of human XIST alleles on active and inactive X chromosomes present in somatic cell hybrids and fibroblast cultures. The replication timing method was based on the isolation of newly-replicated DNA from cells pulse-labeled with bromodexyuridine and separated by flow cytometry into different fractions of the cell cycle. Two human x hamster hybrid cell lines that contain active X chromosomes were found to replicate the inactive XIST allele early in S, similar to the active MIC2 gene. Active XIST alleles replicated late in S for three different hybrids containing inactive X chromosomes. MIC2 is expressed from both active and inactive X chromosomes and was found to replicate early in both active and inactive X hybrids. Male fibroblasts replicated XISt early in S, while both early and late peaks of replication were observed in female cells. The unusual replication patterns of active and inactive X alleles of XIST are similar to that of the autosomal H19 gene: late replication for active alleles and early replication for inactive alleles. This pattern of replication is a dramatic exception to the general rule that active genes replicate early in S phase. In addition to similar replication patterns, both H19 and XIST are subject to genomic imprinting and encode functional RNA products. Late replication timing for the active alleles of these genes may have functional significance. Further studies at these loci may help to eluidate the role of replication timing in the epigenetic control of imprinting, gene activity, and gene function.

• OSTI ID: 133383
• 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
CELL CYCLE
DNA REPLICATION
GENES
GENETIC MAPPING
HUMAN X CHROMOSOME
POLYMERASE CHAIN REACTION
SOMATIC CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION