Low XIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra X chromosome / 亚洲男科学杂志(英文版)

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.

Cold-induced alteration in the global structure of the male sex chromosome of In1BM2(reinverted) of Drosophila melanogaster is associated with increased acetylation of histone 4 at lysine 16.

In Drosophila melanogaster, dosage compensation occurs through hypertranscription of sex-linked genes in males. The hypertranscription involves acetylation of histone 4 at lysine 16 (H4K16) on amale X-chromosome, brought about by a histone acetyltransferase encoded by the dosage compensation gene, males absent on the first (mof). We report a phenomenon in the strain In(1)B(M2)(reinverted) of D. melanogaster where the global structure of the male X-chromosome can be altered at the third instar larval stage through a 4-h cold shock at 12+/-1 degrees C. We show that the cold shock results in a transient hyperacetylation of H4K16 and an increased expression of MOF. Control proteins H4 acetylated at lysine 5, and the dosage compensation gene msl-2, do not show any change in expression after cold shock. Cytology of the male X-chromosome at different time points during cold shock and recovery, suggests that the hyperacetylation of H4 at lysine 16 causes the X-chromosome to corkscrew into itself, thereby achieving the cold-induced change in the higher order structure of the male polytene X-chromosome. Our studies suggest a role for H4K16 in maintaining the structure of the male X-chromosome in Drosophila.

Binding affinity of leucine-containing chromatin proteins to the polytene X chromosome of Drosophila hydei and its significance.

Association of newly synthesised non-histone chromosomal protein to the polytene X chromosome of larval salivary glands of D. hydei has been examined by autoradiographic procedure using 3H-leucine. It has been observed that 3H-leucine labelling pattern is inhibited in presence of puromycin. Results further reveal that there is a reasonable concordance between the binding affinity of newly synthesized protein on the single X chromosome of the male and paired X's of the female. A sitewise analysis of 3H-leucine labelling reveals that although 3H-leucine incorporation pattern are not strictly comparable with 3H-RNA synthesis pattern observed under in vivo transcription condition, the labelling pattern with 3H-leucine are not merely the reflection of mass distribution of protein in the polytene chromosomes. Certain aspects of regulation in the organisation of male and female X chromosome in Drosophila by de novo synthesis of protein are discussed.

Mosaic pattern of X-chromosomal transcription in a strain of Drosophila melanogaster with aneuploid X chromosome.

Organisation and template activity pattern of salivary gland chromosomes of a segmental male aneuploid of D. melanogaster, carrying duplication for the segment 8C-20F of X chromosome, have been examined by in situ transcription. In an earlier study [Chatterjee, Chromosoma 91 (1985) 259], it was suggested that in male aneuploids, up to an additional length of 8C-20F, the template activity of X chromosome tends to remain at a male level and beyond that level shifts towards female level. A large scale search of the template activity pattern of the aneuploid carrying dp.(8C-20F) clearly indicates that presence of the duplication fragment to X in the normal karyotype (1X2A) lead to a varying degree of condensation of euchromatic regions of entire X chromosome (X + X fragment 8C-20F) starting from 'male' level, over a wide range of 'intermediate' level to a normal 'female' level. In this study, the individual cells of the aneuploid appeared to display their own state of X condensation and transcription. Although in the aneuploid, X chromosomal activity is not determined by a purely quantitative effect of X vs. autosomal material (X:A ratio = 0.81), the 8C-20F segment of X chromosome must contain some major elements concerned with the signal given by X:A ratio for X chromosome differentiation.