Binding of TFIIIC to SINE Elements Controls the Relocation of Activity-Dependent Neuronal Genes to Transcription Factories

Autor: Thomas A. Down, Cristina Policarpi, Antonella Riccio, Alessandro Coatti, Bart C. Jongbloets, Luca Crepaldi, William T. Sherlock
Rok vydání: 2013
Předmět:
Transcription factories
Cancer Research
Mouse
Transcription
Genetic
Regulatory Sequences
Nucleic Acid
Epigenesis
Genetic
Histones
DNA transposons
Mice
Molecular cell biology
0302 clinical medicine
Transcription (biology)
Transcriptional regulation
Promoter Regions
Genetic
Genetics (clinical)
Short Interspersed Nucleotide Elements
Regulation of gene expression
Genetics
0303 health sciences
Neuronal Morphology
General transcription factor
Chromosome Biology
Cell Differentiation
Acetylation
Animal Models
Cellular Structures
Chromatin
Epigenetics
Histone modification
Transposons
Research Article
Chromosome Structure and Function
lcsh:QH426-470
DNA transcription
Biology
03 medical and health sciences
Model Organisms
Transcription Factors
TFIII
Animals
Gene silencing
Molecular Biology
Ecology
Evolution
Behavior and Systematics
030304 developmental biology
Cell Nucleus
Promoter
lcsh:Genetics
Cellular Neuroscience
Gene expression
030217 neurology & neurosurgery
Developmental Biology
Neuroscience
Zdroj: PLoS Genetics, Vol 9, Iss 8, p e1003699 (2013)
PLoS Genetics
ISSN: 1553-7404
DOI: 10.1371/journal.pgen.1003699
Popis: In neurons, the timely and accurate expression of genes in response to synaptic activity relies on the interplay between epigenetic modifications of histones, recruitment of regulatory proteins to chromatin and changes to nuclear structure. To identify genes and regulatory elements responsive to synaptic activation in vivo, we performed a genome-wide ChIPseq analysis of acetylated histone H3 using somatosensory cortex of mice exposed to novel enriched environmental (NEE) conditions. We discovered that Short Interspersed Elements (SINEs) located distal to promoters of activity-dependent genes became acetylated following exposure to NEE and were bound by the general transcription factor TFIIIC. Importantly, under depolarizing conditions, inducible genes relocated to transcription factories (TFs), and this event was controlled by TFIIIC. Silencing of the TFIIIC subunit Gtf3c5 in non-stimulated neurons induced uncontrolled relocation to TFs and transcription of activity-dependent genes. Remarkably, in cortical neurons, silencing of Gtf3c5 mimicked the effects of chronic depolarization, inducing a dramatic increase of both dendritic length and branching. These findings reveal a novel and essential regulatory function of both SINEs and TFIIIC in mediating gene relocation and transcription. They also suggest that TFIIIC may regulate the rearrangement of nuclear architecture, allowing the coordinated expression of activity-dependent neuronal genes.
Author Summary In neurons, acetylation of histones and other epigenetic modifications influence gene expression in response to synaptic activity. Genes that are concomitantly expressed in response to stimulation are transcribed at specific nuclear foci, known as transcription factories (TFs) that are enriched with active RNA Polymerase II and often include specific transcription factors. Here, we show a novel regulatory role for Short Interspersed Elements (SINEs) located in the proximity of activity-regulated genes. SINEs represent a new class of regulatory sequences that function as coordinators of depolarization-dependent transcription. Binding of the general transcription factor TFIIIC to SINEs regulates activity-dependent transcription, relocation of inducible genes to transcription factories and dendritogenesis. Our study provides new fundamental insights into the mechanisms by which relocation of inducible genes to transcription factories and changes of nuclear architecture coordinate the transcriptional program in response to neuronal activity.
Databáze: OpenAIRE
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