TY - JOUR
T1 - An 840 kb distant upstream enhancer is a crucial regulator of catecholamine-dependent expression of the Bdnf gene in astrocytes
AU - Makeyev, Eugene
AU - Zhuravskaya, Anna
N1 - Funding Information:
This work has been supported by Estonian Research Council (institutional research funding IUT19‐18 and grant PRG805), European Union through the European Regional Development Fund (Project No. 2014–2020.4.01.15‐0012) and H2020‐MSCA‐RISE‐2016 (Grant EU734791) and BBSRC (grants BB/R001049/1 and BB/V006258/1). This work has also been partially supported by TUT Institutional Development Program for 2016–2022 Graduate School in Clinical medicine receiving funding from the European Regional Development Fund under program ASTRA 2014–2020.4.01.16‐0032 in Estonia. We thank Epp Väli for technical assistance; Kaie Uustalu for contribution in the early stage of the project; Florencia Cabrera‐Cabrera and Olga Jasnovidova for critical reading of the manuscript.
Funding Information:
This work has been supported by Estonian Research Council (institutional research funding IUT19-18 and grant PRG805), European Union through the European Regional Development Fund (Project No. 2014–2020.4.01.15-0012) and H2020-MSCA-RISE-2016 (Grant EU734791) and BBSRC (grants BB/R001049/1 and BB/V006258/1). This work has also been partially supported by TUT Institutional Development Program for 2016–2022 Graduate School in Clinical medicine receiving funding from the European Regional Development Fund under program ASTRA 2014–2020.4.01.16-0032 in Estonia. We thank Epp Väli for technical assistance; Kaie Uustalu for contribution in the early stage of the project; Florencia Cabrera-Cabrera and Olga Jasnovidova for critical reading of the manuscript.
Publisher Copyright:
© 2023 The Authors. GLIA published by Wiley Periodicals LLC.
PY - 2023/8/25
Y1 - 2023/8/25
N2 - Brain-derived neurotrophic factor (BDNF) plays a fundamental role in the developing and adult nervous system, contributing to neuronal survival, differentiation, and synaptic plasticity. Dysregulation of BDNF synthesis, secretion or signaling has been associated with many neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Although the transcriptional regulation of the Bdnf gene has been extensively studied in neurons, less is known about the regulation and function of BDNF in non-neuronal cells. The most abundant type of non-neuronal cells in the brain, astrocytes, express BDNF in response to catecholamines. However, genetic elements responsible for this regulation have not been identified. Here, we investigated four potential Bdnf enhancer regions and based on reporter gene assays, CRISPR/Cas9 engineering and CAPTURE-3C-sequencing we conclude that a region 840 kb upstream of the Bdnf gene regulates catecholamine-dependent expression of Bdnf in rodent astrocytes. We also provide evidence that this regulation is mediated by CREB and AP1 family transcription factors. This is the first report of an enhancer coordinating the transcription of Bdnf gene in non-neuronal cells.
AB - Brain-derived neurotrophic factor (BDNF) plays a fundamental role in the developing and adult nervous system, contributing to neuronal survival, differentiation, and synaptic plasticity. Dysregulation of BDNF synthesis, secretion or signaling has been associated with many neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Although the transcriptional regulation of the Bdnf gene has been extensively studied in neurons, less is known about the regulation and function of BDNF in non-neuronal cells. The most abundant type of non-neuronal cells in the brain, astrocytes, express BDNF in response to catecholamines. However, genetic elements responsible for this regulation have not been identified. Here, we investigated four potential Bdnf enhancer regions and based on reporter gene assays, CRISPR/Cas9 engineering and CAPTURE-3C-sequencing we conclude that a region 840 kb upstream of the Bdnf gene regulates catecholamine-dependent expression of Bdnf in rodent astrocytes. We also provide evidence that this regulation is mediated by CREB and AP1 family transcription factors. This is the first report of an enhancer coordinating the transcription of Bdnf gene in non-neuronal cells.
UR - http://www.scopus.com/inward/record.url?scp=85168867231&partnerID=8YFLogxK
U2 - 10.1002/glia.24463
DO - 10.1002/glia.24463
M3 - Article
SN - 0894-1491
VL - 72
SP - 90
EP - 110
JO - Glia
JF - Glia
IS - 1
ER -