Epigenetic profile of the euchromatic region of human Y chromosome

Abstract

The genome of a multi-cellular organism acquires various functional capabilities in different cell types by means of distinct chromatin modifications and packaging states. Acquired during early development, the cell type-specific epigenotype is maintained by cellular memory mechanisms that involve epigenetic modifications. Here we present the epigenetic status of the euchromatic region of the human Y chromosome that has mostly been ignored in earlier whole genome epigenetic mapping studies. Using ChIP-on-chip approach, we mapped H3K9ac, H3K9me3, H3K27me3 modifications and CTCF binding sites while DNA methylation analysis of selected CpG islands was done using bisulfite sequencing. The global pattern of histone modifications observed on the Y chromosome reflects the functional state and evolutionary history of the sequences that constitute it. The combination of histone and DNA modifications, along with CTCF association in some cases, reveals the transcriptional potential of all protein coding genes including the sex-determining gene SRY and the oncogene TSPY. We also observe preferential association of histone marks with different tandem repeats, suggesting their importance in genome organization and gene regulation. Our results present the first large scale epigenetic analysis of the human Y chromosome and link a number of cis-elements to epigenetic regulatory mechanisms, enabling an understanding of such mechanisms in Y chromosome linked disorders.

Epigenetics of sex determination and gonadogenesis

“…To illustrate, in order to understand how chromatin reorganizes during gonadogenesis, Maatouk et al () performed genome‐wide DNaseI hypersensitivity mapping (DNaseI‐seq), an assay that allows locating and characterizing regulatory regions of the genome based on the property that they are depleted of nucleosomes. Another interesting approach is the study of Singh et al (). Using a ChIP‐on‐chip approach, they mapped different histone modifications, including H3K9ac, H3K9me3, and H3K27me3, and CTCF (a.k.a.…”

“…Another interesting approach is the study of Singh et al (2011). Using a ChIP-on-chip approach, they mapped different histone modifications, including H3K9ac, H3K9me3, and H3K27me3, and CTCF (a.k.a.…”

High frequency ofTTTY2-like gene-related deletions in patients with idiopathic oligozoospermia and azoospermia

“…While some autosomal or X‐linked genes seem to be involved in various spermatogenic stages (Dohle et al ., ; Kukuvitis et al ., ), there is an increasing evidence that several important genes are located on the long arm of the Y chromosome, and particularly in the azoospermia factor (AZF) regions AZFa, AZFb and AZFc (Navarro‐Costa et al ., ; Massart et al ., ). Located in these regions, there are some gene families referred as the DAZ , TSPY , RBMY and TTTY genes (Arnemann et al ., ; Ma et al ., ; Krausz & Fellous, ; Skaletsky et al ., ; Singh et al ., ). Deletions in the AZF region have been suspected to be one of the main genetic causes of male infertility (Tiepolo & Zuffardi, ; Schnieders et al ., ; Vogt et al ., ; Pryor et al ., ; Ferlin et al ., ; Simoni et al ., ; Krausz et al ., ; Hsu et al ., ; EAU, ; Singh et al ., ).…”

Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

“…Recently, Singh et al (23) demonstrated by large-scale epigenomic analysis the transcriptional potential of all protein-coding genes on the Y-chromosome including the SRY and the oncogene TSPY . According to the authors, the GBY locus may be hypomethylated in gonadoblastomas, resulting in overexpression of the TSPY and TTTY genes (24,25).…”