Myc-associated zinc-finger protein, encoded by the MAZ gene, has been identified as a new factor impacting on gene regulation and three-dimensional genome organization. US researchers found that MAZ, together with the CCCTC-binding factor CTCF, insulates active and repressed genes within Hox gene clusters. Hox genes encode transcription factors that regulate activity of other genes during development.

Proper embryonic development depends on the precise regulation of cell-type-specific gene expression. This is critically influenced by chromatin structure and three-dimensional architecture of the genome. Transcriptional repressors like CTCF play an important role in these processes. In its insulating function, CTCF protects genes from inappropriate activity of regulatory elements (enhancers), thus repressing gene expression. In their study published in Nature Genetics, the researchers coupled a genome-wide CRISPR knockout screen with biochemical approaches to look for genes that act similarly to and in combination with CTCF to regulate gene expression. From a list of hundreds of candidates, they identified MAZ as a co-factor in CTCF insulation that colocalizes with CTCF at chromatin boundaries and, similar to CTCF, interacts with the cohesin component RAD21. They also showed that MAZ loss alters Hox gene expression, chromatin domains and global genome organization.