DOI: 10.1073/pnas.96.7.3836. Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain

Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain

10.1073/pnas.96.7.3836

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Dosage compensation in mammals occurs by X inactivation, a silencing mechanism regulated in cis by the X inactivation center (Xic). In response to developmental cues, theXicorchestrates events of X inactivation, including chromosome counting and choice, initiation, spread, and establishment of silencing. It remains unclear what elements make up theXic.We previously showed that theXicis contained within a 450-kb sequence that includesXist, an RNA-encoding gene required for X inactivation. To characterize theXicfurther, we performed deletional analysis across the 450-kb region by yeast-artificial-chromosome fragmentation and phage P1 cloning. We testedXicdeletions for cis inactivation potential by using a transgene (Tg)-based approach and found that an 80-kb subregion also enacted somatic X inactivation on autosomes.XistRNA coated the autosome but skipped theXicTg, raising the possibility that X chromosome domains escape inactivation by excludingXistRNA binding. The autosomes became late-replicating and hypoacetylated on histone H4. A deletion of theXist5′ sequence resulted in the loss of somatic X inactivation without abolishingXistexpression in undifferentiated cells. Thus,Xistexpression in undifferentiated cells can be separated genetically from somatic silencing. Analysis of multipleXicconstructs and insertion sites indicated that long-rangeXiceffects can be generalized to different autosomes, thereby supporting the feasibility of a Tg-based approach for studying X inactivation.

Bibliography

Lee, J. T., Lu, N., & Han, Y. (1999). Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain. Proceedings of the National Academy of Sciences, 96(7), 3836â3841.

Authors 3

Jeannie T. Lee (first)
Naifung Lu (additional)
Yoon Han (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:39 a.m.)
Deposited	1 year, 7 months ago (Jan. 3, 2024, 11:59 p.m.)
Indexed	1 month, 2 weeks ago (July 12, 2025, 6:43 p.m.)
Issued	26 years, 4 months ago (March 30, 1999)
Published	26 years, 4 months ago (March 30, 1999)
Published Online	26 years, 4 months ago (March 30, 1999)
Published Print	26 years, 4 months ago (March 30, 1999)

Funders 0

None

BibTeX

@article{Lee_1999, title={Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.7.3836}, DOI={10.1073/pnas.96.7.3836}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lee, Jeannie T. and Lu, Naifung and Han, Yoon}, year={1999}, month=mar, pages={3836–3841} }

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