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Significance Eukaryotic genomes are compacted into chromosomes, in which heterochromatin is generally considered to be distinct from euchromatin in chromosomal packaging levels and locations. InDrosophila , heterochromatin is mainly found in pericentric and telomeric regions. In this study, we show that heterochromatin landscapes that interspersed in euchromatic arms are counteracted by CDK12, a major RNA polymerase II C-terminal domain kinase. After the depletion of CDK12, heterochromatin enrichment can be observed on euchromatic arms, especially on the X chromosome, which leads to transcriptional attenuation in targeted genes and defects in neuronal functions. Our findings provide insights into the regulation of heterochromatin domain in the natural chromosomal context and suggest a chromatin regulatory role of CDK12 in neuronal functions.

Heterochromatin remodeling by CDK12 contributes to learning in Drosophila