Widespread transcription at neuronal activity-regulated enhancers.
We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified approximately 12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.
Kim
Tae-Kyung
TK
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Hemberg
Martin
M
Gray
Jesse M
JM
Costa
Allen M
AM
Bear
Daniel M
DM
Wu
Jing
J
Harmin
David A
DA
Laptewicz
Mike
M
Barbara-Haley
Kellie
K
Kuersten
Scott
S
Markenscoff-Papadimitriou
Eirene
E
Kuhl
Dietmar
D
Bito
Haruhiko
H
Worley
Paul F
PF
Kreiman
Gabriel
G
Greenberg
Michael E
ME
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D050882:CREB-Binding Protein / Q000378:metabolism; D016384:Consensus Sequence / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter; D016762:Genes, fos / Q000235:genetics; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D050882:CREB-Binding Protein; D003598:Cytoskeletal Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; D012319:RNA Polymerase II; D022661:RNA, Untranslated; C533005:Npas4 protein, mouse; C092069:activity regulated cytoskeletal-associated protein
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