Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

ChIP-Seq for Pbx1 in the mouse E12.5 ventral midbrain

ABSTRACT: Investigations into the roles for Pbx1 and its transcriptional network in dopaminergic neuron development and Parkinson's Disease One sample each for Pbx1, IgG, and input

ORGANISM(S): Mus musculus

SUBMITTER: Sten Linnarsson

PROVIDER: E-GEOD-82098 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease.

Villaescusa J Carlos JC Li Bingsi B Toledo Enrique M EM Rivetti di Val Cervo Pia P Yang Shanzheng S Stott Simon Rw SR Kaiser Karol K Islam Saiful S Gyllborg Daniel D Laguna-Goya Rocio R Landreh Michael M Lönnerberg Peter P Falk Anna A Bergman Tomas T Barker Roger A RA Linnarsson Sten S Selleri Licia L Arenas Ernest E

The EMBO journal 20160628 18

Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is sufficient to generate mDAn from human stem cells. Mechanistically, PBX1 plays a dual role in transcription by directly repressing or activa ...[more]

PMID: 27354364

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Project description:The proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. M-BM- In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification. Examination of Ascl1 and Ptf1a genome-wide binding in developing neural tube.

Dataset Information

ChIP-Seq for Pbx1 in the mouse E12.5 ventral midbrain

Publications

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease.

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