CHROMO domain readers: A rainbow of opportunities

Chromatin regulators have a prestigious function in controlling the proper development and maintenance of homeostasis. Aberrant chromatin remodeling and epigenetic modification lead to dysregulated gene expression, which eventually causes diverse human diseases. The chromodomain (CD)-containing family proteins are among the most important chromatin modulators—especially chromatin readers that preferentially recognize and regulate methylated histones. The human genome encodes 41 CDs in 32 different proteins, which can be further grouped into three major subfamilies. Here, we review current insights regarding this large CD-containing protein family in regulating cellular proliferation and development, chromatin dynamics and maintenance, DNA damage response and repair, transcription regulation, and immune homeostasis. We highlight the uncovered physiological roles of CD-containing proteins in distinct human maladies ranging from developmental disorders to cancers as well as recent progress in developing and testing inhibitors targeting CD-containing proteins for treating human diseases.