The Bühler lab previously discovered the ChAHP complex which represses short interspersed element (SINE) retrotransposons and consists of three proteins, including the transcription factor ADNP. Now, they found a second complex called ChAHP2, in which ADNP is replaced by ADNP2, and that this complex suppresses the activity of endogenous retroviruses (ERVs) and long interspersed elements (LINEs). It targets them by binding H3K9 trimethylated histones, an acitivity which also ChAHP possesses. Inactivation of ChAHP on top of ChAHP2 ablation, leads to further derepression of ERVs and LINEs. Their findings have been published in the article "ChAHP2 and ChAHP control diverse retrotransposons by complementary activities" in Genes & Development.
Abstract
Retrotransposon control in mammals is an intricate process that is effectuated by a broad network of chromatin regulatory pathways. We previously discovered ChAHP, a protein complex with repressive activity against short interspersed element (SINE) retrotransposons that is composed of the transcription factor ADNP, chromatin remodeler CHD4, and HP1 proteins. Here we identify ChAHP2, a protein complex homologous to ChAHP, in which ADNP is replaced by ADNP2. ChAHP2 is predominantly targeted to endogenous retroviruses (ERVs) and long interspersed elements (LINEs) via HP1B-mediated binding of H3K9 trimethylated histones. We further demonstrate that ChAHP also binds these elements in a manner mechanistically equivalent to that of ChAHP2 and distinct from DNA sequence-specific recruitment at SINEs. Genetic ablation of ADNP2 alleviates ERV and LINE1 repression, which is synthetically exacerbated by additional depletion of ADNP. Together, our results reveal that the ChAHP and ChAHP2 complexes function to control both nonautonomous and autonomous retrotransposons by complementary activities, further adding to the complexity of mammalian transposon control.
Read the Publication in Genes & Development (Open Access)
Abstract, figure and title from Ahel, Pandey, Schwaiger et al (2024) Genes & Development published under a CC BY 4.0 license.