Dataset of differentially expressed genes in mouse P12 testes in response to the loss of ATRX in Sertoli cells

Bagheri‐Fam, Stefan; Alankarage, Dimuthu; Frost, Emily R; Harley, Vincent R.

doi:10.1016/j.dib.2022.108230

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…On the other hand, ATRX can promote gene transcription through the incorporation of histone H3.3 and facilitating RNA PolII elongation through G-rich sequences 40 , 41 . In testes, ATRX regulates imprinted genes 42 associates with the androgen receptor and facilitates transcription of its target genes 43 . ATRX also promotes the expression of α-globin by negatively regulating the histone variant macroH2A 44 .…”

Section: Introductionmentioning

confidence: 99%

Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination in male mice

Rowland,

Jiang,

Shafiq

et al. 2023

Nat Commun

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Myelin, an extension of the oligodendrocyte plasma membrane, wraps around axons to facilitate nerve conduction. Myelination is compromised in ATR-X intellectual disability syndrome patients, but the causes are unknown. We show that loss of ATRX leads to myelination deficits in male mice that are partially rectified upon systemic thyroxine administration. Targeted ATRX inactivation in either neurons or oligodendrocyte progenitor cells (OPCs) reveals OPC-intrinsic effects on myelination. OPCs lacking ATRX fail to differentiate along the oligodendrocyte lineage and acquire a more plastic state that favors astrocytic differentiation in vitro and in vivo. ATRX chromatin occupancy in OPCs greatly overlaps with that of the chromatin remodelers CHD7 and CHD8 as well as H3K27Ac, a mark of active enhancers. Overall, our data indicate that ATRX regulates the onset of myelination systemically via thyroxine, and by promoting OPC differentiation and suppressing astrogliogenesis. These functions of ATRX identified in mice could explain white matter pathogenesis observed in ATR-X syndrome patients.

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Section: Introductionmentioning

confidence: 99%

Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination in male mice

Rowland,

Jiang,

Shafiq

et al. 2023

Nat Commun

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Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination

Rowland

Jiang

Shafiq

et al. 2022

Preprint

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SummaryNeurodevelopmental disorders are often characterized by abnormal production of myelin, an extension of the oligodendrocyte plasma membrane wrapped around axons to facilitate nerve conduction. However, the molecular mechanisms that control myelination during brain development are incompletely resolved. Here, we provide evidence that loss of ATRX, encoded by the gene mutated in the ATR-X intellectual disability syndrome, leads to myelin deficits in the mouse CNS. While postnatal systemic thyroxine administration can improve myelination, the rescue is incomplete, pointing to additional roles of ATRX in this process. We show that targeted inactivation of ATRX in postnatal oligodendrocyte progenitor cells (OPCs), but not in neurons, also leads to myelination deficits, demonstrating cell-intrinsic effects of ATRX deficiency. A subset of ATRX-null OPCs express lower levels of oligodendrocyte specification and differentiation markers, including the basic helix-loop-helix Olig2 transcription factor. Mechanistically, we provide evidence that ATRX occupies genomic sites in OPCs marked by H3K27Ac, CHD7 and CHD8 and demonstrate that reduced Olig2 expression is associated with decreased H3K27Ac. Finally, our data suggest that ATRX-null OPCs acquire a more plastic state and can exhibit astrocyte-like features in vitro and in vivo, supporting a model in which ATRX regulates the onset of myelination by promoting OPC identity and suppressing astrogliogenesis. These previously unrecognized functions of ATRX might explain white matter pathogenesis in ATR-X syndrome patients.

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Dataset of differentially expressed genes in mouse P12 testes in response to the loss of ATRX in Sertoli cells

Cited by 2 publications

References 10 publications

Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination in male mice

Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination in male mice

Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination

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