Heterochromatin remodeling by CDK12 contributes to learning in Drosophila

Lixia Pan, Wenbing Xie, Kai Le Li, Zhihao Yang, Jiang Xu, Wenhao Zhang, Lu Ping Liu, Xingjie Ren, Zhimin He, Junyu Wu, Jin Sun, Hui Min Wei, Daliang Wang, Wei Xie, Wei Li, Jian Quan Ni, Fang Lin Sun

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Abstract

Dynamic regulation of chromatin structure is required to modulate the transcription of genes in eukaryotes. However, the factors that contribute to the plasticity of heterochromatin structure are elusive. Here, we report that cyclin-dependent kinase 12 (CDK12), a transcription elongation-Associated RNA polymerase II (RNAPII) kinase, antagonizes heterochromatin enrichment in Drosophila chromosomes. Notably, loss of CDK12 induces the ectopic accumulation of heterochromatin protein 1 (HP1) on euchromatic arms, with a prominent enrichment on the X chromosome. Furthermore, ChIP and sequencing analysis reveals that the heterochromatin enrichment on the X chromosome mainly occurs within long genes involved in neuronal functions. Consequently, heterochromatin enrichment reduces the transcription of neuronal genes in the adult brain and results in a defect in Drosophila courtship learning. Taken together, these results define a previously unidentified role of CDK12 in controlling the epigenetic transition between euchromatin and heterochromatin and suggest a chromatin regulatory mechanism in neuronal behaviors.

Original languageEnglish (US)
Pages (from-to)13988-13993
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number45
DOIs
Publication statusPublished - Nov 10 2015

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