Model for how ATRX might influence gene expression. ATRX is part of a multiprotein complex that uses the energy of ATP to remodel chromatin 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 or of recruitment of transcription factors (directly or indirectly) that alter gene expression. ATRX function may be associated with its presence at one of its target nuclear locations (eg, heterochromatin, ribosomal DNA repeats, PML bodies) in addition to euchromatic sites. Potential points for interaction between ATRX and MDS, leading to a more severe hematologic phenotype than in ATR-X syndrome, include the multiprotein complex, of which ATRX is a part; transcription factors, whose binding to DNA is affected by the ATRX complex; and epigenetic modifications of histone-associated DNA, leading to alterations in local chromatin conformation.