Journal
CELL REPORTS
Volume 21, Issue 1, Pages 47-59Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.09.014
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Funding
- Juan de la Cierva - Incorporacion from the Spanish Ministry of Economy and Competitivity [MINECO]
- MINECO (European Regional Development Fund [ERDF]) [SAF2014-60233-JIN]
- MINECO (ERDF) [SAF2014-56197-R, PCIN-2015-192-C02-01, ERA-Net NEURON8-2015, SEV-2013-0317]
- Generalitat Valenciana [PROMETEO/2016/006]
- NARSAD Independent Investigator grant from the Brain & Behavior Research Foundation [21941]
- Alicia Koplowitz Foundation
- NIH [NS089896, MH096066]
- Farrehi Family Foundation
- Formacion de Personal Investigador'' fellowships (Spanish Ministry of Economy and Competitivity [MINECO])
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During development, chromatin-modifying enzymes regulate both the timely establishment of cell-typespecific gene programs and the coordinated repression of alternative cell fates. To dissect the role of one such enzyme, the intellectual-disability-linked lysine demethylase 5C (Kdm5c), in the developing and adult brain, we conducted parallel behavioral, transcriptomic, and epigenomic studies in Kdm5c-null and forebrain-restricted inducible knockout mice. Together, genomic analyses and functional assays demonstrate that Kdm5c plays a critical role as a repressor responsible for the developmental silencing of germline genes during cellular differentiation and in fine-tuning activity-regulated enhancers during neuronal maturation. Although the importance of these functions declines after birth, Kdm5c retains an important genome surveillance role preventing the incorrect activation of non-neuronal and cryptic promoters in adult neurons.
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