Heterochromatin remodeling by CDK12 contributes to learning in Drosophila.
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.
School of Medicine, Tsinghua University, Beijing 100084, China;
Lixia
L
Pan
Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing 100871, China;
Wenbing
W
Xie
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120/200092, China;
Kai-Le
KL
Li
School of Medicine, Tsinghua University, Beijing 100084, China;
Zhihao
Z
Yang
School of Medicine, Tsinghua University, Beijing 100084, China;
Jiang
http://orcid.org/0000-0002-6933-5453
J
Xu
Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Wenhao
W
Zhang
School of Medicine, Tsinghua University, Beijing 100084, China;
Lu-Ping
LP
Liu
School of Medicine, Tsinghua University, Beijing 100084, China;
Xingjie
X
Ren
School of Medicine, Tsinghua University, Beijing 100084, China;
Zhimin
Z
He
School of Medicine, Tsinghua University, Beijing 100084, China;
Junyu
J
Wu
School of Medicine, Tsinghua University, Beijing 100084, China;
Jin
J
Sun
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120/200092, China;
Hui-Min
HM
Wei
School of Medicine, Tsinghua University, Beijing 100084, China;
Daliang
D
Wang
Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Wei
W
Xie
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120/200092, China;
Wei
W
Li
School of Medicine, Tsinghua University, Beijing 100084, China; nijq@tsinghua.edu.cn flsun@mail.tsinghua.edu.cn.
Jian-Quan
JQ
Ni
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120/200092, China; School of Medicine, Tsinghua University, Beijing 100084, China; nijq@tsinghua.edu.cn flsun@mail.tsinghua.edu.cn.
Fang-Lin
FL
Sun
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology*; D006570:Heterochromatin / Q000235:genetics / Q000502:physiology*; D047468:Immunoprecipitation; D007858:Learning / Q000502:physiology*; D008969:Molecular Sequence Data; D017830:Octoxynol; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000033:anatomy & histology / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D006570:Heterochromatin; D017830:Octoxynol; D018844:Cyclin-Dependent Kinases
HP1; RNAPII C-terminal domain kinase; epigenetic transition; histone H3 on Lys9 methylation; neuronal function