The AFF (AF4/FMR2) family includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the cell nucleus and are involved in regulation of gene expression [, ].In humans, AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs) [, ].This entry also includes Drosophila AF4 protein homologue Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila [].This entry represents the C-terminal domain homology domain (CHD) that is conserved among AF4/FMR2 family proteins, including AFF1, AFF2, AFF3, and AFF4. This domain consists of eight helices and is distantly related to tetratricopeptide repeat motifs. The CHD domain mediates the formation of an AFF4 homodimer or an AFF1-AFF4 heterodimer. []. This domain is essential for AFF4 interaction with Transcription Start Site (TSS)-associated histone H3K27 whose acetylation signals SEC to regulate transcriptional elongation of the ESR1 gene []. Depletion of AFF4 reduces expression of ESR1, and, consequently inhibits breast cancer cell growth [].
