Biology subjects

Makowski, C. E.

Publications and source records attributed to Makowski, C. E..

2 recordsLinked to original sources

bioRxiv2022

Competition for H2A.Z between genes and repetitive elements establishes response to anti-viral immune activation

Activation of endogenous retroviruses leads to widespread transcriptional reprograming, affecting innate immune activation, metabolic control, and development. We find that the histone variant H2A.Z plays a central role in orchestrating these responses. Stimulating retroviral expression in zebrafish embryos causes H2A.Z to exit developmental gene promoters, which become silent, and to accumulate specifically at primed repetitive elements, which are pre-marked by H3K27ac and H3K9me3. Remarkably, this rewiring is greatly influenced by total H2A.Z abundance, and developmental consequences of retrovirus activation are mitigated by H2A.Z over-expression. Our results uncover mechanisms whereby H2A.Z levels determine sensitivity to retroviral activation, and repetitive elements function as a nuclear sink to dramatically influence total transcriptional output. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/486614v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@275f37org.highwire.dtl.DTLVardef@dc2d9aorg.highwire.dtl.DTLVardef@135f599org.highwire.dtl.DTLVardef@18f290c_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2020

Genome-wide Chromatin Accessibility is Restricted by ANP32E

Genome-wide chromatin state underlies gene expression potential and cellular function. Epigenetic features and nucleosome positioning contribute to the accessibility of DNA, but widespread regulators of chromatin state are largely unknown. Our study investigates how control of genomic H2A.Z localization by ANP32E contributes to chromatin state in mouse fibroblasts. We define H2A.Z as a universal chromatin accessibility factor, and demonstrate that through antagonism of H2A.Z, ANP32E restricts genome-wide DNA access. In the absence of ANP32E, H2A.Z accumulates at promoters in a hierarchical manner. H2A.Z initially localizes downstream of the transcription start site, and if H2A.Z is already present downstream, additional H2A.Z accumulates upstream. This hierarchical H2A.Z accumulation coincides with improved nucleosome positioning, heightened transcription factor binding, and increased expression of neighboring genes. Thus, ANP32E dramatically influences genome-wide chromatin accessibility through refinement of H2A.Z patterns, providing a means to reprogram chromatin state and to hone gene expression levels.

genetics↗