Modulation of Developmentally Regulated Gene Expression Programs through Targeting of Polycomb and Trithorax Group Proteins

Brand, Marjorie; Dilworth, F. Jeffrey

doi:10.1002/9781118349045.ch26

Cited by 1 publication

(1 citation statement)

References 223 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2C, rec G9a specifically pulled down rec Jarid1a (but not the control rec Ubc4), demonstrating a direct interaction between these proteins. Taken together, these results indicate that G9a, GLP, and Jarid1a are tightly associated within the same protein complex that is distinct from the core PRC2 complex containing Ezh2 and Suz12 (32).…”

Section: Resultsmentioning

confidence: 65%

Maintenance of gene silencing by the coordinate action of the H3K9 methyltransferase G9a/KMT1C and the H3K4 demethylase Jarid1a/KDM5A

Chaturvedi

Somasundaram

Singh

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Chromatin remodeling is essential for controlling the expression of genes during development. The histone-modifying enzyme G9a/KMT1C can act both as a coactivator and a corepressor of transcription. Here, we show that the dual function of G9a as a coactivator vs. a corepressor entails its association within two distinct protein complexes, one containing the coactivator Mediator and one containing the corepressor Jarid1a/KDM5A. Functionally, G9a is important in stabilizing the Mediator complex for gene activation, whereas its repressive function entails a coordinate action with the histone H3 lysine 4 (H3K4) demethylase Jarid1a for the maintenance of gene repression. The essential nature of cross-talk between the histone methyltransferase G9a and the demethylase Jarid1a is demonstrated on the embryonic E y -globin gene, where the concurrent introduction of repressive histone marks (dimethylated H3K9 and dimethylated H3K27) and removal of activating histone mark (trimethylated H3K4) is required for maintenance of gene silencing. Taken together with our previous demonstration of cross-talk between UTX and MLL2 to mediate activation of the adult β maj -globin gene, these data suggest a model where “active” and “repressive” cross-talk between histone-modifying enzymes coexist on the same multigene locus and play a crucial role in the precise control of developmentally regulated gene expression.

show abstract

Section: Resultsmentioning

confidence: 65%