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Mamm Genome. 2016 Jun;27(5-6):225-36. doi: 10.1007/s00335-016-9630-2. Epub 2016 Apr 18.

Robertsonian translocations modify genomic distribution of γH2AFX and H3.3 in mouse germ cells.

Author information

1
Department of Human Genetics, McGill University, Montreal, QC, Canada.
2
Genetics and Biochemistry Branch, NIDDK, NIH, Bethesda, MD, USA.
3
Research Institute of McGill University Health Centre, Montreal, QC, Canada.
4
Department of Human Genetics, McGill University, Montreal, QC, Canada. anna.naoumova@mcgill.ca.
5
Research Institute of McGill University Health Centre, Montreal, QC, Canada. anna.naoumova@mcgill.ca.
6
Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada. anna.naoumova@mcgill.ca.

Abstract

Heterozygosity for Robertsonian translocations hampers pairing and synapsis between the translocated chromosome and its normal homologs during meiotic prophase I. This causes meiotic silencing of unsynapsed chromatin in pericentromeric regions. Several lines of evidence suggest that autosomal asynapsis leads to meiotic arrest in males and two underlying mechanisms have been proposed: (1) reactivation of the X and Y chromosomes due to competition for silencing factors and (2) meiotic silencing of genes that are located in the unsynapsed regions and are essential for meiotic progression. The latter mechanism requires that asynapsis and meiotic silencing spread beyond the p-arms of the normal homologs into gene-rich regions. We used chromatin immunoprecipitation assays to determine whether histones γH2AFX and H3.3, both marks of asynapsis and meiotic silencing, are enriched in gene-rich regions of the translocated chromosomes and their homologs in the spermatocytes of heterozygous carriers of Robertsonian translocations. We also asked if γH2AFX and H3.3 enrichment was reduced at the X chromosome and if γH2AFX and H3.3 enrichment was higher on the normal homolog. Our data show that γH2AFX enrichment extends as far as 9-15 Mb of the annotated genomic sequence of the q-arms of the translocated chromosomal trivalents and that both γH2AFX and H3.3 levels are reduced over the X chromosome. Our data are also suggestive of an asymmetry in γH2AFX and H3.3 enrichment with a bias toward the non-translocated homolog.

PMID:
27090237
DOI:
10.1007/s00335-016-9630-2
[Indexed for MEDLINE]

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