Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons
Abstract
DLX transcription factors (TFs) are master regulators of the developing vertebrate brain, driving forebrain GABAergic neuronal differentiation. Ablation of Dlx1&2 alters expression of genes that are critical for forebrain GABAergic development. We integrated epigenomic and transcriptomic analyses, complemented with in situ hybridization (ISH), and in vivo and in vitro studies of regulatory element (RE) function. This revealed the DLX-organized gene regulatory network at genomic, cellular, and spatial levels in mouse embryonic basal ganglia. DLX TFs perform dual activating and repressing functions; the consequences of their binding were determined by the sequence and genomic context of target loci. Our results reveal and, in part, explain the paradox of widespread DLX binding contrasted with a limited subset of target loci that are sensitive at the epigenomic and transcriptomic level to Dlx1&2 ablation. The regulatory properties identified here for DLX TFs suggest general mechanisms by which TFs orchestrate dynamic expression programs underlying neurodevelopment.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Institutes of Health (NIH); NIMH; NIGMS
- OSTI Identifier:
- 1557912
- Alternate Identifier(s):
- OSTI ID: 1623649; OSTI ID: 1650070
- Grant/Contract Number:
- AC02-05CH11231; R37/R01 MH049428; R35 GM119831; R01HG003988
- Resource Type:
- Published Article
- Journal Name:
- Cell Reports
- Additional Journal Information:
- Journal Name: Cell Reports Journal Volume: 28 Journal Issue: 8; Journal ID: ISSN 2211-1247
- Publisher:
- Elsevier
- Country of Publication:
- Netherlands
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Cell biology; DLX; transcription factor; enhancers; regulatory element; genome; transcriptional circuits; chromatin; histone; ChIP-seq; development; ganglionic eminence; GABA neuron; basal ganglia; telencephalon
Citation Formats
Lindtner, Susan, Catta-Preta, Rinaldo, Tian, Hua, Su-Feher, Linda, Price, James D., Dickel, Diane E., Greiner, Vanille, Silberberg, Shanni N., McKinsey, Gabriel L., McManus, Michael T., Pennacchio, Len A., Visel, Axel, Nord, Alex S., and Rubenstein, John L. R. Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons. Netherlands: N. p., 2019.
Web. doi:10.1016/j.celrep.2019.07.022.
Lindtner, Susan, Catta-Preta, Rinaldo, Tian, Hua, Su-Feher, Linda, Price, James D., Dickel, Diane E., Greiner, Vanille, Silberberg, Shanni N., McKinsey, Gabriel L., McManus, Michael T., Pennacchio, Len A., Visel, Axel, Nord, Alex S., & Rubenstein, John L. R. Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons. Netherlands. https://doi.org/10.1016/j.celrep.2019.07.022
Lindtner, Susan, Catta-Preta, Rinaldo, Tian, Hua, Su-Feher, Linda, Price, James D., Dickel, Diane E., Greiner, Vanille, Silberberg, Shanni N., McKinsey, Gabriel L., McManus, Michael T., Pennacchio, Len A., Visel, Axel, Nord, Alex S., and Rubenstein, John L. R. Thu .
"Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons". Netherlands. https://doi.org/10.1016/j.celrep.2019.07.022.
@article{osti_1557912,
title = {Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons},
author = {Lindtner, Susan and Catta-Preta, Rinaldo and Tian, Hua and Su-Feher, Linda and Price, James D. and Dickel, Diane E. and Greiner, Vanille and Silberberg, Shanni N. and McKinsey, Gabriel L. and McManus, Michael T. and Pennacchio, Len A. and Visel, Axel and Nord, Alex S. and Rubenstein, John L. R.},
abstractNote = {DLX transcription factors (TFs) are master regulators of the developing vertebrate brain, driving forebrain GABAergic neuronal differentiation. Ablation of Dlx1&2 alters expression of genes that are critical for forebrain GABAergic development. We integrated epigenomic and transcriptomic analyses, complemented with in situ hybridization (ISH), and in vivo and in vitro studies of regulatory element (RE) function. This revealed the DLX-organized gene regulatory network at genomic, cellular, and spatial levels in mouse embryonic basal ganglia. DLX TFs perform dual activating and repressing functions; the consequences of their binding were determined by the sequence and genomic context of target loci. Our results reveal and, in part, explain the paradox of widespread DLX binding contrasted with a limited subset of target loci that are sensitive at the epigenomic and transcriptomic level to Dlx1&2 ablation. The regulatory properties identified here for DLX TFs suggest general mechanisms by which TFs orchestrate dynamic expression programs underlying neurodevelopment.},
doi = {10.1016/j.celrep.2019.07.022},
journal = {Cell Reports},
number = 8,
volume = 28,
place = {Netherlands},
year = {Thu Aug 01 00:00:00 EDT 2019},
month = {Thu Aug 01 00:00:00 EDT 2019}
}
https://doi.org/10.1016/j.celrep.2019.07.022
Web of Science
Figures / Tables:
Figures / Tables found in this record: