H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function

Pal, Debosree; Patel, Manthan; Boulet, Fanny; Jayakumar, S.; Grant, Olivia A; Branco, Miguel R.; Basu, Srinjan; Zabet, Nicolae Radu; Scaffidi, Paola; Pradeepa, Madapura M.

doi:10.1101/2022.04.29.488986

Cited by 10 publications

(15 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, we find on chrXR of D. pseudoobscura an significant ( P < 0.05, Wilcoxon test) excess of not only genes but also TEs that have turned into a DC or PE state, relative to the homologous autosomes of D. melanogaster or other autosomes of D. pseudoobscura ( Figure 4d ). This could be due to the byproduct of the spreading of the DC complex and its consequential PTM H4K16ac along the chrXR 56 . Alternatively, as shown before 21 , some newly propagated TEs on the chrXR can mediate the spread of DC.…”

Section: Resultsmentioning

confidence: 99%

Development and Evolution of Drosophila Chromatin Landscape in a 3D genome context

Ali

Younas

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

Chromatin states of genes and transposable elements (TEs) dictated by combinations of various histone modifications comprise key information for understanding the mechanisms of genome organization and regulation. However, little is known about the principles of their dynamic changes during development and evolution in a three-dimensional genome context. To address this, we study Drosophila pseudoobscura, a Drosophila model species that diverged from D. melanogaster about 25 million years ago. We collected 71 epigenomic datasets targeting 11 histone modification marks and 4 Hi-C datasets, and projected 15 chromatin states across four different developmental stages and two adult tissues. We estimate that before zygotic genome activation, 41% of the genome has already been deposited with histone modifications, while 20% of the rest genome switches from a null state to an active/inactive chromatin state after the zygotic genome activation. Over two thirds of the genomic region exhibit at least one transition between different chromatin states during development. And such transitions on cis-regulatory regions are associated with tissue- or stage-specific formation of chromatin loops or topologically associated domain borders (TABs), as well as specific activation of gene expression. We further demonstrate that while evolutionarily young TEs are preferentially targeted by silencing histone modifications, old TEs are more frequently domesticated as TABs or specific enhancers that further contribute to the genome organization or local gene regulation. Interestingly, this trend is reversed on the newly evolved X chromosome in D. pseudoobscura, due to the acquisition of dosage compensation mechanism. Overall we characterize the developmental and evolutionary dynamics of Drosophila epigenomic states, and highlight the roles of certain TEs of different evolutionary ages in genome organization and regulation.

show abstract

Section: Resultsmentioning

confidence: 99%

Development and Evolution of Drosophila Chromatin Landscape in a 3D genome context

Ali

Younas

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Additionally, histone acetylation also regulates TEs. This was depicted in the enrichment of histone 4 lysine 16 acetylation, and histone 3 lysine 122 acetylations for LINE1 ( Pal et al, 2022 ). While most epigenetic mechanisms are associated with silencing TEs, in this case, histone acetylation facilitated TE transcription ( Pal et al, 2022 ).…”

Section: Transposable Elements and Epigeneticsmentioning

confidence: 96%

“…This was depicted in the enrichment of histone 4 lysine 16 acetylation, and histone 3 lysine 122 acetylations for LINE1 (Pal et al, 2022). While most epigenetic mechanisms are associated with silencing TEs, in this case, histone acetylation facilitated TE transcription (Pal et al, 2022). The mechanisms of these how histone modifications regulate TEs are beginning to be understood.…”

Section: Transposable Elements and Epigeneticsmentioning

confidence: 99%

The Role of Transposable Elements in Sexual Development

Chiang

DeRosa

Park

et al. 2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Up to 50% of most mammalian genomes are made up of transposable elements (TEs) that have the potential to mobilize around the genome. Despite this prevalence, research on TEs is only beginning to gain traction within the field of neuroscience. While TEs have long been regarded as “junk” or parasitic DNA, it has become evident that they are adaptive DNA and RNA regulatory elements. In addition to their vital role in normal development, TEs can also interact with steroid receptors, which are key elements to sexual development. In this review, we provide an overview of the involvement of TEs in processes related to sexual development- from TE activity in the germline to TE accumulation in sex chromosomes. Moreover, we highlight sex differences in TE activity and their regulation of genes related to sexual development. Finally, we speculate on the epigenetic mechanisms that may govern TEs’ role in sexual development. In this context, we emphasize the need to further the understanding of sexual development through the lens of TEs including in a variety of organs at different developmental stages, their molecular networks, and evolution.

show abstract

“…The LTRs of young ERVs are GC-rich sequences (Extended Data Fig. 6), and can generally behave as bona fide, potent enhancers of gene expression, as demonstrated both in classical reverse genetics assays and by in situ inactivation of individual inserts, with subfamilies displaying distinctive tissue-specificity associated with the binding of tissue-specific transcription factors (59,60,(68)(69)(70)(71)(72). Young ERVs inserts are therefore markedly bipotential, having strong enhancer capacity while being also prominent targets for heterochromatinmediated repression (60,65,73).…”

Section: Identifying Core Sets Of Proa and Prob Elements And Mechanis...mentioning

confidence: 99%

ProA and ProB repeat sequences shape genome organization, and enhancers open domains

Bonnet,

Hulo,

Mourad

et al. 2023

Preprint

View full text Add to dashboard Cite

SUMMARYThere is a growing awareness that repeat sequences (RepSeq) - the main constituents of the human genome - are also prime players in its organization. Here we propose that the genome should be envisioned as a supersystem with three main subsystems, each composed of functionally redundant, cooperating elements. We define herein ProA and ProB RepSeqs as sequences that promote either the A/euchromatin or the B/heterochromatin compartment. ProA and ProB RepSeqs shape A/B partitioning, such that the relative proportions of ProA and ProB RepSeqs determine the propensity of a chromosome segment to adopt either an A or a B configuration. In human, core ProA RepSeqs are essentially made of Alu elements, whereas core ProB RepSeqs consist of young L1 and some Endogenous Retroviruses (ERVs) as well as a panel of AT-rich microsatellites and pericentromeric and telomeric satellites. Additionally, RepSeqs with more indefinite character and, importantly, their derivatives known as “transcriptional enhancers”, can shift between ProA and ProB functions and thus act to open or close specific chromatin domains depending on the cellular context. In this framework, genes and their promoters appear as a special class of RepSeqs that, in their active, transcribed state, reinforce the openness of their surroundings. Molecular mechanisms involve cooperativity between ProB elements, presumably underpinned by the condensate-like properties of heterochromatin, which ProA elements oppose in several ways. We provide strong arguments that altered CpG methylation patterns in cancer including a marked loss in the B compartment, result primarily from a global imbalance in the process of CpG methylation and its erasure. Our results suggest that the resulting altered methylation and impaired function of ProB RepSeqs globally weaken the B compartment, rendering it more plastic, which in turn may confer fate plasticity to the cancer cell.

show abstract

H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function

Cited by 10 publications

References 86 publications

Development and Evolution of Drosophila Chromatin Landscape in a 3D genome context

Development and Evolution of Drosophila Chromatin Landscape in a 3D genome context

The Role of Transposable Elements in Sexual Development

ProA and ProB repeat sequences shape genome organization, and enhancers open domains

Contact Info

Product

Resources

About