Faculty Collaboration Database

Kr??ppel-like factor 11 differentially couples to histone acetyltransferase and histone methyltransferase chromatin remodeling pathways to transcriptionally regulate dopamine D2 receptor in neuronal cells. J Biol Chem 2012 Apr 13;287(16):12723-35

Date

03/01/2012

Pubmed ID

22375010

Pubmed Central ID

PMC3339994

DOI

10.1074/jbc.M112.351395

Scopus ID

2-s2.0-84859776104   29 Citations

Abstract

The importance of Kr??ppel-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-I?-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.

Author List

Seo S, Lomberk G, Mathison A, Buttar N, Podratz J, Calvo E, Iovanna J, Brimijoin S, Windebank A, Urrutia R

Authors

Gwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis Regulatory Proteins
Base Sequence
Cell Cycle Proteins
Cell Differentiation
Chromatin
Dopaminergic Neurons
Down-Regulation
Histone Acetyltransferases
Histone-Lysine N-Methyltransferase
Homeostasis
Humans
Molecular Sequence Data
Neurites
PC12 Cells
Promoter Regions, Genetic
Rats
Receptors, Dopamine D2
Repressor Proteins
Transcription, Genetic