PAR-TERRA directs homologous sex chromosome pairing

  title={PAR-TERRA directs homologous sex chromosome pairing},
  author={Hsueh-Ping Chu and John E Froberg and Barry A. Kesner and Hyun Jung Oh and Fei Ji and Ruslan I. Sadreyev and Stefan F. Pinter and Jeannie T. Lee},
  journal={Nature structural \& molecular biology},
  pages={620 - 631}
In mammals, homologous chromosomes rarely pair outside meiosis. One exception is the X chromosome, which transiently pairs during X-chromosome inactivation (XCI). How two chromosomes find each other in 3D space is not known. Here, we reveal a required interaction between the X-inactivation center (Xic) and the telomere in mouse embryonic stem (ES) cells. The subtelomeric, pseudoautosomal regions (PARs) of the two sex chromosomes (X and Y) also undergo pairing in both female and male cells. PARs… 

Nuclear positioning and pairing of X-chromosome inactivation centers are not primary determinants during initiation of random X-inactivation

It is found that neither nuclear lamina localization nor reduction of Xic homologous pairing influences monoallelic Xist upregulation or choice-making, and transient pairing is associated with biallelic expression, not only at Xist/Tsix but also at other X-linked loci that can escape XCI.

Characterization of telomeric repeat-containing RNA (TERRA) localization and protein interactions in primordial germ cells of the mouse†.

The data indicate that TERRA expression and interactome during PGC development are regulated in a dynamic fashion that is dependent on gestational age and sex.

Revisiting the consequences of deleting the X inactivation center

The essential nature of noncoding Xic elements for the initiation of XCI is reaffirmed, as multiple independent clones carrying heterozygous deletions of the Xic display an inability to up-regulate Xist expression, consistent with a counting defect.

PAR-TERRA is the main contributor to telomeric repeat-containing RNA transcripts in normal and cancer mouse cells.

It is shown that PAR-TERRA molecules account for the majority of TERRA transcripts, displaying an increase of 2 to 4 orders of magnitude compared to the telomeric 18q transcript, and a large overlap between TERRA-interacting proteins in human and mouse cells is presented.

Characterization of Telomeric Repeat-Containing RNA (TERRA) localization and protein interactions in Primordial Germ Cells of the mouse

The results show that, TERRA interacting proteins are determined by sex in both PGCs and somatic cells, and indicate that TERRA expression and interactome during PGC development are regulated in a dynamic fashion that is dependent on gestational age and sex.

Gene regulation in time and space during X-chromosome inactivation

The multiple layers of genetic and epigenetic regulation that underlie initiation of XCI during development and then maintain it throughout life are discussed, in light of the most recent findings in this rapidly advancing field.

Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape

Evidence is provided that megadomains do not precede Xist expression or Xi gene silencing, and it is suggested that Dxz4, Firre, and megadamains are dispensable for Xi silencing and escape from X-inactivation.

Decapping enzyme 1A breaks X-chromosome symmetry by controlling Tsix elongation and RNA turnover

“BioRBP” is developed, an enzymatic RNA-proteomic method that enables probing of low-abundance interactions and an allelic RNA-depletion and -tagging system and reports that DCP1A negatively regulates Tsix RNA abundance by suppressing its transcriptional elongation and RNA stability, thus contributing to X-chromosome inactivation.

The Emerging Roles of TERRA in Telomere Maintenance and Genome Stability

Emerging evidence indicates that a class of long noncoding RNAs transcribed at telomeres, known as TERRA for “TElomeric Repeat-containing RNA,” actively participates in the mechanisms regulating telomere maintenance and chromosome end protection.

DNA–RNA interactions are critical for chromosome condensation in Escherichia coli

It is demonstrated that naRNA4 uniquely acts by forming complexes that may not involve long stretches of DNA–RNA hybrid, which will be of great interest in the chromatin field, providing mechanistic insights into the large-scale organization of DNA.



Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein

It is proposed that pairing requires Ctcf binding and co-transcriptional activity of Tsix and Xite and that the Ctcf-interacting partner, Yy1, is not required.

Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation

It is demonstrated that interchromosomal pairing mediates this communication between X inactivation and X-chromosome inactivation, and proposed that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing.

A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation

These findings demonstrate that, while Xist attracts repressive complexes to the Xi, it actively repels chromosomal architectural factors such as the cohesins from the Xi.

Spreading of X chromosome inactivation via a hierarchy of defined Polycomb stations.

Examining allele-specific binding of Polycomb repressive complex 2 (PRC2) and chromatin composition during XCI and generating a chromosome-wide profile of Xi and Xa (active X) at nucleosome-resolution suggests that XCI is governed by a hierarchy of defined Polycomb stations that spread H3K27 methylation in cis.

The mechanism of meiotic homologue pairing.

  • M. Maguire
  • Biology
    Journal of theoretical biology
  • 1984

Mechanics and Dynamics of X-Chromosome Pairing at X Inactivation

It is shown that soluble DNA-specific binding molecules can be indeed sufficient to induce the spontaneous colocalization of the homologous chromosomes but only when their concentration, or chemical affinity, rises above a threshold value as a consequence of a thermodynamic phase transition.

Telomere-mediated chromosome pairing during meiosis in budding yeast.

It is speculated that telomere-mediated chromosome movement and/or telomeres clustering promote homolog pairing, and that even nonhomologous chromosome ends can promote homologue pairing to a limited extent.

Telomeric RNAs Mark Sex Chromosomes in Stem Cells

It is proposed that telomeric RNAs are tied to cell differentiation and may be used to mark pluripotency and disease, and RNA accumulation increases in Dicer-deficient stem cells, suggesting direct or indirect links to RNAi.

Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation

It is proposed that transient colocalization of Xics may be necessary for a cell to determine Xic number and to ensure the correct initiation of X inactivation.

The pluripotency factor, Oct4, interacts with Ctcf and also controls X-chromosome pairing and counting

It is shown that Oct4 (also known as Pou5f1) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing and counting, the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X- chromosome reprogramming.