Abstract
Jarid1c, an X-linked gene coding for a histone demethylase, plays an important role in brain development and function. Notably, JARID1C mutations cause mental retardation and increased aggression in humans. These phenotypes are consistent with the expression patterns we have identified in mouse brain where Jarid1c mRNA was detected in hippocampus, hypothalamus, and cerebellum. Jarid1c expression and associated active histone marks at its 5′end are high in P19 neurons, indicating that JARID1C demethylase plays an important role in differentiated neuronal cells. We found that XX mice expressed Jarid1c more highly than XY mice, independent of their gonadal types (testes versus ovaries). This increased expression in XX mice is consistent with Jarid1c escape from X inactivation and is not compensated by expression from the Y-linked paralogue Jarid1d, which is expressed at a very low level compared to the X paralogue in P19 cells. Our observations suggest that sex-specific expression of Jarid1c may contribute to sex differences in brain function.
Highlights
Mutations in JARID1C are one of the leading causes of X-linked mental retardation [1,2]
To better understand the pathophysiology of mental retardation and increased aggression caused by JARID1C mutations [1,2,8], it is important to determine where JARID1C accumulates in the brain
Jarid1c is expressed in specific brain regions Using in situ hybridization with an antisense riboprobe, Jarid1c mRNA was detected throughout brain sections from male and female adult mice
Summary
Mutations in JARID1C are one of the leading causes of X-linked mental retardation [1,2]. Mouse Jarid1c and human JARID1C encode a highly conserved JmjC-domain protein that catalyzes the removal of methyl groups from tri- or di-methylated lysine 4 on histone H3 [3,4,5]. Since this histone modification is associated with enhanced gene activity, demethylation of H3 lysine 4 by JARID1C leads to transcriptional repression [6]. To better understand the pathophysiology of mental retardation and increased aggression caused by JARID1C mutations [1,2,8], it is important to determine where JARID1C accumulates in the brain. In the present study we determined the pattern of expression of Jarid1c in mouse brain sections by in situ hybridization
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have