Genomic profiling of PML bodies reveals transcriptional regulation by PML bodies through the DNMT3A exclusion

Abstract

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Y chromosome damage underlies testicular abnormalities in ATR-X syndrome

“…Therefore, loss of ATRX in these tissues will lead to chromosome-wide defects. That in mice a specific PML NB can directly interact with Yp was recently demonstrated in mouse embryonic stem cells (mESC) (Kurihara et al, 2020). In these cells, a 300 kb region (YS300) near the Y chromosome telomere that contains the Yp probe used in our study is frequently associated with a large PML NB (Kurihara et al, 2020).…”

“…That in mice a specific PML NB can directly interact with Yp was recently demonstrated in mouse embryonic stem cells (mESC) (Kurihara et al, 2020). In these cells, a 300 kb region (YS300) near the Y chromosome telomere that contains the Yp probe used in our study is frequently associated with a large PML NB (Kurihara et al, 2020). This PML NB forms a specific complex with YS300 to regulate the expression of neighbouring clustered genes such as Uty and Ddx3y.…”

“…Since GATA2 can interact with the PML protein via its zinc finger region shared by all GATA proteins (Tsuzuki et al, 2000), GATA4 may also interact with PML. Another unique feature of Yp is the presence of specific inverted repeats within YS300 that are not homologous to other sequences in the genome (Kurihara et al, 2020). It is therefore possible that these sequences may also play a unique role in the formation of a PML NB specifically at this chromosomal region.…”

“…Recently, it has been demonstrated that a 300 kb region (YS300) on the short arm of the Y chromosome (Yp) is frequently associated with a large PML NB in mouse embryonic stem cells (Kurihara et al, 2020).Therefore, we investigated whether the single chromosome at the GATA4 foci may be the Y chromosome. We performed Immuno-FISH for GATA4 and two different Y probes, a 73.6 kb Yp probe (Chr Y: 112,036-184,662) that detects the 300 kb region associated with the reported PML NB (Kurihara et al, 2020) and a Yq probe that detects a 1.8 kb repeat dispersed over a 48 Mb region across the long arm of the Y chromosome (Chr Y: 4,173,194,425). Immuno-FISH for GATA4 and the Yp probe revealed that Yp co-localized completely or partially with the GATA4 signal in 81% of control and 93% of ScAtrxKO Sertoli cells (Fig.…”

“…Recently, the short arm of the Y chromosome has been identified as a region to which PML NBs frequently bind (Kurihara et al, 2020). No function of PML NBs during sex development or in differences/disorders of sex development (DSD) has been demonstrated to date.…”