[The role of ribonucleoprotein complexes of mRNA in translation (author's transl)].
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Histone-like nucleoid structuring protein H-NS plays a pivotal role in orchestrating bacterial chromatin and regulating horizontal gene transfer (HGT) elements. In response to environmental signals, H-NS undergoes dynamic post-translational modifications (PTMs) that resemble the epigenetic codes of eukaryotic histones. This review explores how environmental cues regulate PTMs at specific sites within distinct domains of H-NS, thereby modulating its oligomerization and DNA-binding capabilities to reprogram bacterial responses. Notably, HGT elements commonly encode counter-silencing factors, including PTM-modifying enzymes, that counteract H-NS repression. We propose that combinatorial PTM patterns on H-NS form the bacterial histone-like epigenetic code, regulating the expression of HGT elements. Collectively, these interactions establish a sophisticated network of silencing and counter-silencing mechanisms that drive bacterial genome evolution.
MOTIVATION: Histone modifications play an important role in transcription regulation. Although the general importance of some histone modifications for transcription regulation has been previously established, the relevance of others and their interaction is subject to ongoing research. By training Machine Learning models to predict a gene's expression and explaining their decision making process, we can get hints on how histone modifications affect transcription. In previous studies, trained models were either hardly explainable or the models were trained solely on the abundance of histone modifications. Based on other studies, which used histone modification patterns, rather than their abundance, to identify potential regulatory elements, we hypothesize the histone modification pattern in a gene's promoter to be more predictive for gene expression. We used an optimization algorithm to extract predictive histone modification profiles. RESULTS: Our algorithm called PatternChrome achieved an average area under curve (AUC) score of 0.9029 over 56 samples for binary classification, outperforming all previous algorithms for the same task. We explained the models decisions to deduce the effect of specific features, certain histone modifications or promoter positions on transcription regulation. Although the predictive histone modification patterns were extracted for each sample separately, they can be used to predict gene expression in other samples, implying that the created patterns are largely generalizable. Interestingly, the impact of histone modifications on gene regulation appears predominantly indifferent to cellular specificity. Through explanation of the classifier's decisions, we substantiate established literature knowledge while concurrently revealing novel insights into the intricate landscape of transcriptional regulation via histone modification. AVAILABILITY AND IMPLEMENTATION: The code for the PatternChrome algorithm, the scripts for the analyses and the required data can be found at (https://gitlab.gwdg.de/MedBioinf/generegulation/patternchrome).
Histone genes in D. hydei are organized in tandemly repeated clusters., accomodating in total 120-140 repeat units. We cloned one of the repeat units and analysed the nucleotide sequence. The repeat unit has a size of 5.1 x 10(3) base-pairs and contains one copy of each of the genes coding for the core histones and one copy coding for the histone H1. In the promoter regions of the genes we identified the presumptive cap sites and TATA boxes. Two additional sequence elements are shared by all five Drosophila hydei histone genes in the cluster. The sequence CCCTCT/G1 is found in the region upstream of the presumptive CAP sites. The sequence element AGTGAA occurs downstream of the presumptive cap sites and is, in contrast to the promoter element, also seen in the histone genes of Drosophila melanogaster. Cell-cycle dependent regulation of transcription of the Drosophila histone genes may be different from that in other eukaryotes since sequence elements involved in the regulation of cell-cycle dependent transcription are absent. Also other regulatory elements for transcription differ from those of other genes. The highly conserved H1-specific promoter sequence AAACACA and the H2B specific promoter sequence ATTTGCAT, which are involved in the cell-cycle dependent transcription of those histone genes in eukaryotes, are missing in the Drosophila genes. However at the 3' end of the genes the palindrome and the purine-rich region, both conserved sequence elements in histone genes of eukaryotes, are present. The spacer regions show a simple sequence organization. The silent site substitution rate between the coding regions of the D. hydei and D. melanogaster histone genes is at least 1.5 times higher for Drosophila than for sea urchin histone genes.
The linear arrangement and lengths of the spacers and coding regions in the two nonallelic histone gene variant clusters of L. pictus are remarkably homologous by R loop analysis and are similar in general topography to the histone gene repeat units of other sea urchins examined to date. No interventing sequences were detected. The coding regions of these two histone gene variants share considerable sequence homology; however, there are areas of nonhomology in every spacer region and the lengths of the nonhomologous spacers between the H2A and H1 genes are not the same for the two repeat unit classes (inter-gene heterogeneity). Combining length measurements obtained with both R loops and heteroduplexes suggests that the DNA sequences of the analogous leader regions for the two H1 mRNAs are nonhomologous. Similar observations were made for the H4 leader sequences, as well as the trailer region on H2B. S. purpuratus spacer DNA segments share little sequence homology with L. pictus; however, the analgous coding (and possibly flanking) regions have conserved their sequences. The various coding and spacer regions within a repeat unit do not share DNA sequences. Thus certain areas in the sea urchin histone gene repeat units have been highly conserved during evolution, while other areas have been allowed to undergo considerable sequence change not only between species but within a species.
The genes coding for the H3 and H4 histones of Saccharomyces cerevisiae have been isolated by recombinant DNA cloning. The genes were detected in a bacteriophage lambda library of the yeast genome by hybridization with plasmids containing the cloned Psammechinus miliaris sea urchin histone genes (pCH7) and the cloned Drosophila histone genes (cDM500). Two non-allelic sets of the H3 and H4 genes have been isolated. Each set consists of one H3 gene and one H4 gene arranged as a divergently transcribed pair separated by an intergene spacer DNA. The histone genes were located on the cloned yeast fragments by S1 nuclease mapping, as was a gene (SMT1) of unknown function that does not code for a histone but is closely linked to one of the histone sets. Sequence homology between the two non-allelic sets is confined to the coding regions of the respective genes while the flanking DNA and intergene spacer DNA are extensively divergent. Cellular RNA homologous to the histone genes, including transcribed non-coding sequences unique to each of the four genes, was detected by S1 mapping, thus demonstrating that all four genes are transcribed in vegetative cells.
From a mouse genomic DNA library we have isolated sequences containing the entire coding region for histone H1(0) mRNA, flanked by several kb at both the 3' and 5' ends. Deletions of the 5' upstream region ligated to the chloramphenicol acetyltransferase (CAT)-encoding gene as a reporter, have shown that a region from bp -400 to -600 is necessary and sufficient for efficient transcription. We have also shown that treatment of F9 teratocarcinoma cells with retinoic acid and cyclic AMP (which differentiates F9 cells to parietal endoderm) clearly increases CAT activity several times over the level found in untreated F9 cells. This increase was observed in transient, as well as in stably transfected cells. Analysis of the deletions in differentiating cells indicates that the element responsible for the observed increase in CAT activity, is contained within the first 700 bp upstream from the H1(0) mRNA cap site.
A genomic clone containing a novel closely linked human histone H2A/H2B gene pair has been isolated and sequenced along with extensive 5' and 3' flanking regions. Both genes are devoid of introns and code for core histone proteins. The nucleotide sequences are 84% and 87% homologous to the coding regions of a human genomic H2A and H2B gene, respectively. A comparison of the nucleotide-derived amino acid sequences shows that the histone H2A protein corresponds to the human H2A.1 subtype, whereas the H2B histone gene predicts an H2B protein sequence which is almost identical to the histone H2B.2 variant from human and bovine obtained by direct protein sequencing. The 3' flanking regions contain previously identified conserved sequence elements thought to be involved in transcription termination and processing of replication-dependent histone gene poly(A)- mRNAs. Primer extension analyses of the histone mRNAs encoded within this clone demonstrate that both genes are divergently transcribed from a 313 bp intergene promoter region. The spatial arrangement and orientation of two TATA-boxes, four CAAT-boxes, and one H2B-box within this region suggests that the linked genes share common promoter elements for transcriptional regulation.