Preprint Article Version 2 This version is not peer-reviewed

Low RNA Binding Strength of Human X Chromosome May Explain X Chromosome Inactivation

Version 1 : Received: 31 October 2018 / Approved: 2 November 2018 / Online: 2 November 2018 (14:42:07 UTC)
Version 2 : Received: 7 November 2018 / Approved: 8 November 2018 / Online: 8 November 2018 (11:10:53 UTC)

How to cite: Ji, N.; Yan, L.; Song, Z.; Liu, S.; Liu, S.; Yang, S.; Cao, H.; Wang, X.; Lv, Z. Low RNA Binding Strength of Human X Chromosome May Explain X Chromosome Inactivation. Preprints 2018, 2018110066 (doi: 10.20944/preprints201811.0066.v2). Ji, N.; Yan, L.; Song, Z.; Liu, S.; Liu, S.; Yang, S.; Cao, H.; Wang, X.; Lv, Z. Low RNA Binding Strength of Human X Chromosome May Explain X Chromosome Inactivation. Preprints 2018, 2018110066 (doi: 10.20944/preprints201811.0066.v2).

Abstract

Two X chromosomes of female mammals randomly inactivate one of paternal or maternal X chromosome in early embryonic development and all the daughter cells produced from these cells retain the same feature of X chromosome inactivation, which is called X chromosome inactivation (XCI). Studying the mechanisms of XCI is important for understanding epigenetic that plays an important role in age-associated diseases. The previous studies have demonstrated that binding of RNAs and DNAs may play a role in activating gene expression. In this paper, our study aims to explore whether the mechanisms of XCI involve the RNA binding strength to X chromosome DNAs. The bioinformatics analyses based on big data were used to analyze the simulated binding strength of RNAs (RNA binding strength) to 23 chromosomes (including X chromosome and 22 human autosomes) and the characteristics of repetitive sequences in the X-inactivation centre. The results revealed that RNA binding strength of the long arm of the X chromosome that is almost entirely inactivated in XCI was significantly lower than that of all autosomes and the short arm of X chromosome, meanwhile the RNA binding strengths of inactivation regions in X chromosome were significantly lower than that of regions escaping from XCI. Different repetitive sequence clusters within the center of XCI presented a cross distribution characteristic. To further prove whether the repetitive sequences in human X chromosome involve in XCI, we cloned long interspersed element (LINE-1, L1) and short interspersed element (Alu) from human Xq13, the center of XCI, and constructed expression vectors carrying sense-antisense combination repetitive sequences (L1s or Alus). Effects of combined L1 or combined Alu sequences on expression of EGFP reporter gene were examined in stably transfected HeLa cells, which simulates the effects of repetitive sequences located on chromosomes. The results of experiments revealed transcribed L1 repetitive sequences activated EGFP reporter gene expression, so did the Alus. The experiment results suggested repetitive sequences activated genes by interaction of transcribed RNAs and DNAs. Since the binding of RNAs and DNAs can activate gene, so the low RNA binding strength of human X chromosome may be one of reasons of XCI. The cross distribution characteristics of different repetitive sequence clusters leading to a cascade of gene activation or gene inactivation may be the reason of transcriptional silencing one of the X chromosomes in female mammals.

Subject Areas

Alu; LINE-1 (L1); X-chromosome inactivation (XCI); repetitive sequences; RNA binding strength

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