Convergent Transcriptional Programs Regulate cAMP Levels in C. elegans GABAergic Motor Neurons

Publication date: Available online 12 October 2017
Source:Developmental Cell
Author(s): Bin Yu, Xiaolin Wang, Shuai Wei, Tao Fu, Emmanuel Enoch Dzakah, Ahmed Waqas, Walter W. Walthall, Ge Shan
Both transcriptional regulation and signaling pathways play crucial roles in neuronal differentiation and plasticity. Caenorhabditis elegans possesses 19 GABAergic motor neurons (MNs) called D MNs, which are divided into two subgroups: DD and VD. DD, but not VD, MNs reverse their cellular polarity in a developmental process called respecification. UNC-30 and UNC-55 are two critical transcription factors in D MNs. By using chromatin immunoprecipitation with CRISPR/Cas9 knockin of GFP fusion, we uncovered the global targets of UNC-30 and UNC-55. UNC-30 and UNC-55 are largely converged to regulate over 1,300 noncoding and coding genes, and genes in multiple biological processes, including cAMP metabolism, are co-regulated. Increase in cAMP levels may serve as a timing signal for respecification, whereas UNC-55 regulates genes such as pde-4 to keep the cAMP levels low in VD. Other genes modulating DD respecification such as lin-14, irx-1, and oig-1 are also found to affect cAMP levels.

Graphical abstract

Teaser

Yu et al. demonstrate that UNC-30 and UNC-55 converge to target ∼1,300 genes using ChIP-seq on endogenously tagged proteins. Multiple processes, including cAMP metabolism, are co-regulated. Increase in cAMP may regulate the timing of DD respecification, whereas UNC-55 keeps cAMP low in VD via regulation of targets such as pde-4.


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