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Euchromatic and heterochromatic behavior of the human X2 chromosome in cell cycle and cell development

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Summary

The eu- and heterochromatic behavior of the late replicating X chromosome in the cell cycle was investigated with a double labeling method by means of H3- and C14-thymidine. It was ascertained that the X chromosome decondenses in retardation after mitosis and appears for a short time as sex chromatin. In cells with a sufficiently long cell cycle, a heterochromatization can occur again during interphase. In cells with a short cell cycle the X chromosome condenses only precociously before mitosis and becomes heterochromatic. Whereas the formation of the mitotic sex chromatin depends on the cell cycle, the interphasic sex chromatin is widely independent of the cell cycle. Examination of living fibroblasts with phase contrast microscopy confirms the results obtained by the double labeling method.

It is concluded from the autoradiographic replication pattern, the condensational behavior in prophase, and sex chromatin findings among X fragments, that the short arm of the X chromosome is euchromatic during interphase and that the interphasic sex chromatin is formed only by the long arm of the X chromosome.

It follows from the findings, which argue for and against the X inactivation, that the Lyon hypothesis (1962) should be modified by the following points: 1. The X chromosome is genetically active in the euchromatic condition. 2. The activity is of a regulative kind. 3. The differentiation into the early- and late-replicating X chromosome takes place not during embryogenesis, but already during the first cell division of the zygote. 4. The supplementary hypothesis of Lyon (1962) that single structural genes are on the X chromosomes or that structural gene activity occurs before “inactivation” cannot be correct.

Zusammenfassung

Mit einer Doppelmarkierungsmethode von H3- und C14-Thymidin wurde das eu- und heterochromatische Verhalten des spätreplizierenden X-Chromosoms im Zellcyclus untersucht. Es wurde festgestellt, daß das X-Chromosom nach der Mitose verzögert dekondensiert und für kurze Zeit als Geschlechtschromatin erscheint. In Zellen mit genügend langem Zellcyclus kann dann während der Interphase wieder eine Heterochromatisation erfolgen. In Zellen mit kurzem Zellcyclus kondensiert das X-Chromosom erst vor der Mitose vorzeitig und wird heterochromatisch. Während die Bildung des mitotischen Geschlechtschromatins vom Zellcyclus abhängt, ist die Entstehung des interphasischen Geschlechtschromatins vom Zellcyclus weitgehend unabhängig. Phasenkontrastuntersuchungen an lebenden Fibroblasten bestätigen im wesentlichen die Ergebnisse mit der Doppelmarkierungs-methode.

Aus dem autoradiographischen Repliktionsmuster, der chromosomalen Kondensation während der Prophase und Geschlechtschromatinbefunden bei X-Fragmenten wird geschlossen, daß der kurze Arm des X-Chromosoms während der Interphase euchromatisch ist und das interphasische Geschlechtschromatin nur vom langen Arm des X-chromosoms gebildet wird.

Aus den Befunden, welche für und gegen die X-Inaktivierung sprechen, ergibt sich, daß die Lyon-Hypothese (1962) in den folgenden Punkten modifiziert werden muß: 1. Das X-Chromosom ist im euchromatischen Zustand genetisch aktiv. 2. Die Aktivität ist regulativer Art. 3. Die Differenzierung in früh- und spätreplizierendes X-Chromosom tritt nicht erst während der Embryogenese ein, sondern schon während der ersten Zellteilung der Zygote. 4. Die Zusatzhypothesen von Lyon (1962), daß sich einzelne strukturelle Gene auf dem X-Chromosom befinden oder eine strukturelle Genaktivität vor der “Inaktivierung” besteht, können nicht stimmen.

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  1. Institut für Humangenetik der Universität Göttingen, Gottingen, Germany

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Back, F. Euchromatic and heterochromatic behavior of the human X2 chromosome in cell cycle and cell development. Humangenetik 25, 315–329 (1974). https://doi.org/10.1007/BF00336907

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