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Krüppel-like Factor 11 Differentially Couples to Histone Acetyltransferase and Histone Methyltransferase Chromatin Remodeling Pathways to Transcriptionally Regulate Dopamine D2 Receptor in Neuronal Cells
Krüppel-like Factor 11 Differentially Couples to Histone Acetyltransferase and Histone Methyltransferase Chromatin Remodeling Pathways to Transcriptionally Regulate Dopamine D2 Receptor in Neuronal Cells
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Background: Chromatin-mediated events utilized by Krüppel-Like factors in neurons remain undefined. Results: Krüppel-Like factor 11 couples to antagonistic chromatin pathways (p300 versus heterochromatin protein 1) to regulate the dopamine D2 receptor gene. Conclusion: This is the first description of mechanisms underlying Krüppel-like factor-mediated functions in neurons. Significance: This knowledge expands our understanding of chromatin-mediated mechanisms that influence homeostasis in highly specialized cells.<br />The importance of Krüppel-like factor (KLF)-mediated transcriptional pathways in the biochemistry of neuronal differentiation has been recognized relatively recently. Elegant studies have revealed that KLF proteins are important regulators of two major molecular and cellular processes critical for neuronal cell differentiation: neurite formation and the expression of neurotransmitter-related genes. However, whether KLF proteins mediate these key processes in a separate or coordinated fashion remains unknown. Moreover, knowledge on the contribution of chromatin dynamics to the biochemical mechanisms utilized by these proteins to perform their function is absent. Here we report the characterization of two antagonistic, chromatin-mediated mechanisms by which KLF11, also known as TIEG2 (transforming growth factor-β-inducible early gene 2) and MODY VII (maturity onset diabetes of the young VII), regulates transcription of the fopamine D2 receptor (Drd2) gene. First, KLF11 activates transcription by binding to a distinct Sp-KLF site within the Drd2 promoter (−98 to −94) and recruiting the p300 histone acetyltransferase. Second, Drd2 transcriptional activation is partially antagonized by heterochromatin protein 1 (HP1), the code reader for histone H3 lysine 9 methylation. Interestingly, KLF11 regulates neurotransmitter receptor gene expression in differentiating neuronal cell populations without affecting neurite formation. Overall, these studies highlight histone methylation and acetylation as key biochemical mechanisms modulating KLF-mediated neurotransmitter gene transcription. These data extend our knowledge of chromatin-mediated biochemical events that maintain key phenotypic features of differentiated neuronal cells.
- Subjects :
- Transcription, Genetic
Molecular Sequence Data
Down-Regulation
p300
Cell Cycle Proteins
Biology
PC12 Cells
Biochemistry
Neurotransmitter Receptors
Chromatin remodeling
03 medical and health sciences
Histone H3
0302 clinical medicine
Neurobiology
Histone H1
Histone H2A
Histone methylation
Neurites
Animals
Homeostasis
Humans
Histone code
Transcription Regulation
Promoter Regions, Genetic
Molecular Biology
Histone Acetyltransferases
030304 developmental biology
Genetics
0303 health sciences
Base Sequence
Receptors, Dopamine D2
Heterochromatin Protein 1 (HP1)
Dopaminergic Neurons
EZH2
Krüppel-like Factor (KLF)
Dopamine Receptors
Cell Differentiation
Histone-Lysine N-Methyltransferase
Cell Biology
Chromatin
Rats
3. Good health
Cell biology
Repressor Proteins
Histone methyltransferase
Histone Methyltransferases
Apoptosis Regulatory Proteins
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 287
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....6f80b285c12bf3cdb5a60009171480b6
- Full Text :
- https://doi.org/10.1074/jbc.m112.351395