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ATRX tolerates activity-dependent histone H3 M-bM-^@M-^\methyl/phos switchingM-bM-^@M-^] to maintain repetitive element silencing in neurons


ABSTRACT: ATRX is a member of the SWI2/SNF2 family of chromatin remodeling proteins and primarily functions at heterochromatic loci via its recognition of M-bM-^@M-^XrepressiveM-bM-^@M-^Y histone modifications (e.g., H3K9me3). Despite significant roles for ATRX during normal neural development, as well as its relationship to human disease, ATRX function in the central nervous system is not well understood. Here, we describe ATRXM-bM-^@M-^Ys ability to recognize an activity-dependent combinatorial histone modification, H3K9me3S10ph, in post-mitotic neurons. In neurons, this M-bM-^@M-^\methyl/phosM-bM-^@M-^] switch occurs exclusively following periods of stimulation and is highly enriched at heterochromatic repeats associated with centromeres. Using a multifaceted approach, we reveal that H3K9me3S10ph bound Atrx represses non-coding transcription of centromeric minor satellite sequences during instances of heightened activity. Our results indicate an essential interaction between ATRX and a previously uncharacterized histone modification in the central nervous system and suggest a potential role for abnormal repetitive element transcription in pathological states manifested by ATRX dysfunction. For Atrx ChIP-seq, IPs were performed on three control vs. three KCl stimulated (all representing biological, and not technical replicates) primary cultured mouse cortical neurons at DIV 8. All samples were normalized to background input levels. For H3K9me3S10phos ChIP-seq, biological singlecates (control vs. forskolin) were analyzed against respective inputs.

ORGANISM(S): Mus musculus

SUBMITTER: Li Shen 

PROVIDER: E-GEOD-64062 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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ATRX tolerates activity-dependent histone H3 methyl/phos switching to maintain repetitive element silencing in neurons.

Noh Kyung-Min KM   Maze Ian I   Zhao Dan D   Xiang Bin B   Wenderski Wendy W   Lewis Peter W PW   Shen Li L   Li Haitao H   Allis C David CD  

Proceedings of the National Academy of Sciences of the United States of America 20141223 22


ATRX (the alpha thalassemia/mental retardation syndrome X-linked protein) is a member of the switch2/sucrose nonfermentable2 (SWI2/SNF2) family of chromatin-remodeling proteins and primarily functions at heterochromatic loci via its recognition of "repressive" histone modifications [e.g., histone H3 lysine 9 tri-methylation (H3K9me3)]. Despite significant roles for ATRX during normal neural development, as well as its relationship to human disease, ATRX function in the central nervous system is  ...[more]

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