A model for how ATRX might influence gene expression.

ATRX is part of a multiprotein complex that uses the energy of ATP hydrolysis to remodel chromatin and/or its associated DNA in a way that affects transcriptional activity at euchromatic loci, including the α globin gene cluster. This interaction may be a result of alteration of the regional distribution of heterochromatin by the complex and/or recruitment of transcription factors (either directly or indirectly) that alter gene expression. ATRX function may be associated with its presence at one of its target nuclear locations (e.g., heterochromatin, ribosomal DNA repeats, and/or PML bodies) in addition to euchromatic sites. Potential points for interaction between ATRX and myelodysplasia (MDS) leading to a more severe hematologic phenotype than in ATR-X syndrome include: (1) the multiprotein complex of which ATRX is a part, (2) the transcription factors whose binding to DNA is affected by the ATRX complex, and (3) epigenetic modifications of histone-associated DNA leading to alterations in chromatin conformation.