RecD plays an essential function during growth at low temperature in the antarctic bacterium Pseudomonas syringae Lz4W

10.1534/genetics.104.038943Genetics17041473-148

Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories

10.26508/LSA.202000864Life Science Alliance42e202000864-e20200086

H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome

In mammals, genome-wide chromatin maps and immuno- fluorescence studies show that broad domains of repressive histone modifications are present on pericentro- meric and telomeric repeats and on the inactive X chromosome. However, only a few autosomal loci such as silent Hox gene clusters have been shown to lie in broad domains of repressive histone modifications. Here we present a ChIP-chip analysis of the repressive H3K27me3 histone modification along chr 17 in mouse embryonic fibroblast cells using an algorithm named broad local enrichments (BLOCs), which allows the identification of broad regions of histone modifications. Our results, confirmed by BLOC analysis of a whole genome ChIP-seq data set, show that the majority of H3K27me3 modifications form BLOCs rather than focal peaks. H3K27me3 BLOCs modify silent genes of all types, plus flanking intergenic regions and their distribution indicates a negative correlation between H3K27me3 and transcription. However, we also found that some nontranscribed gene-poor regions lack H3K27me3. We therefore performed a low-resolution analysis of whole mouse chr 17, which revealed that H3K27me3 is enriched in mega-base-pair-sized domains that are also enriched for genes, short interspersed elements (SINEs) and active histone modifications. These genic H3K27me3 domains alternate with similar-sized gene-poor domains. These are deficient in active histone modifications, as well as H3K27me3, but are enriched for long interspersed elements (LINEs) and long-terminal repeat (LTR) transposons and H3K9me3 and H4K20me3. Thus, an autosome can be seen to contain alternating chromatin bands that predominantly separate genes from one retrotransposon class, which could offer unique domains for the specific regulation of genes or the silencing of autonomous retrotransposons

Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60

Introductory paragraph DNA-double strand break (DSB) repair involves complex interactions between chromatin and repair proteins, including the Tip60 tumor suppressor1. Tip60 is an acetyltransferase which acetylates both histones2-5 and the ATM kinase6, 7. Inactivation of Tip60 leads to defective DNA repair2-4 and increased cancer risk8-11. However, how DNA damage activates Tip60’s acetyltransferase activity is not known. Here, we show that direct interaction between Tip60’s chromodomain and histone H3 trimethylated on lysine 9 (H3K9me3) at DSBs activates Tip60’s acetyltransferase activity. Depletion of intracellular H3K9me3 blocks activation of Tip60’s acetyltransferase activity, resulting in defective ATM activation and widespread defects in DSB repair. In addition, the ability of Tip60 to access H3K9me3 is dependent on the DNA damage induced displacement of HP1β from H3K9me3. Finally, we demonstrate that the mre11-rad50-nbs1 complex targets Tip60 to H3K9me3, and is required to activate Tip60’s acetyltransferase activity. These results reveal a new function for H3K9me3 in co-ordinating activation of Tip60-dependent DNA repair pathways, and imply that aberrant patterns of histone methylation may contribute to cance

The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome

Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and the most common known cause of autism. Most cases of FXS result from the expansion of a CGG·CCG repeat in the 5′ UTR of the FMR1 gene that leads to gene silencing. It has previously been shown that silenced alleles are associated with histone H3 dimethylated at lysine 9 (H3K9Me2) and H3 trimethylated at lysine 27 (H3K27Me3), modified histones typical of developmentally repressed genes. We show here that these alleles are also associated with elevated levels of histone H3 trimethylated at lysine 9 (H3K9Me3) and histone H4 trimethylated at lysine 20 (H4K20Me3). All four of these modified histones are present on exon 1 of silenced alleles at levels comparable to that seen on pericentric heterochromatin. The two groups of histone modifications show a different distribution on fragile X alleles: H3K9Me2 and H3K27Me3 have a broad distribution, whereas H3K9Me3 and H4K20Me3 have a more focal distribution with the highest level of these marks being present in the vicinity of the repeat. This suggests that the trigger for gene silencing may be local to the repeat itself and perhaps involves a mechanism similar to that involved in the formation of pericentric heterochromatin