Cytosine modifications in myeloid malignancies.

Aberrant DNA methylation is a hallmark of many cancers, including the myeloid malignancies acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The discovery of TET-mediated demethylation of 5-methylcytosine (5mC) and technological advancements in next-generation sequencing have permitted the examination of other cytosine modifications, namely 5-hydroxymethylcytosine (5hmC), in these myeloid malignancies on a genome-wide scale. Due to the prominence of mutations in epigenetic modifiers that can influence cytosine modifications in these disorders, including IDH1/2, TET2, and DNMT3A, many recent studies have evaluated the relative levels, distribution, and functional consequences of cytosine modifications in leukemic cells.

Epigenetic deregulation in myeloid malignancies.

Abnormal epigenetic patterning commonly is observed in cancer, including the myeloid malignancies acute myeloid leukemia and myelodysplastic syndromes. However, despite the universal nature of epigenetic deregulation, specific subtypes of myeloid disorders are associated with distinct epigenetic profiles, which accurately reflect the biologic heterogeneity of these disorders. In addition, mutations and genetic alterations of epigenetic-modifying enzymes frequently have been reported in these myeloid malignancies, emphasizing the importance of epigenetic deregulation in the initiation, progression, and outcome of these disorders.

DNA methylation and histone modifications are associated with repression of the inhibin α promoter in the rat corpus luteum.

The transition from follicle to corpus luteum after ovulation is associated with profound morphological and functional changes and is accompanied by corresponding changes in gene expression. The gene encoding the α subunit of the dimeric reproductive hormone inhibin is maximally expressed in the granulosa cells of the preovulatory follicle, is rapidly repressed by the ovulatory LH surge, and is expressed at only very low levels in the corpus luteum. Although previous studies have identified transient repressors of inhibin α gene transcription, little is known about how this repression is maintained in the corpus luteum.