3D or Not 3D: Shaping the Genome during Development

Glaser, Juliane; Mundlos, Stefan

doi:10.1101/cshperspect.a040188

Cited by 12 publications

(6 citation statements)

References 132 publications

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“…For more details on the organization and function of the 3D genome and the methods for understanding how chromatin is folded in the nucleus, we refer the reader to some excellent reviews. [32][33][34][35][36]…”

Section: Structural Variationmentioning

confidence: 99%

Disruption of regulatory domains and novel transcripts as disease‐causing mechanisms

Allou

Mundlos

2023

BioEssays

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Deletions, duplications, insertions, inversions, and translocations, collectively called structural variations (SVs), affect more base pairs of the genome than any other sequence variant. The recent technological advancements in genome sequencing have enabled the discovery of tens of thousands of SVs per human genome. These SVs primarily affect non‐coding DNA sequences, but the difficulties in interpreting their impact limit our understanding of human disease etiology. The functional annotation of non‐coding DNA sequences and methodologies to characterize their three‐dimensional (3D) organization in the nucleus have greatly expanded our understanding of the basic mechanisms underlying gene regulation, thereby improving the interpretation of SVs for their pathogenic impact. Here, we discuss the various mechanisms by which SVs can result in altered gene regulation and how these mechanisms can result in rare genetic disorders. Beyond changing gene expression, SVs can produce novel gene‐intergenic fusion transcripts at the SV breakpoints.

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Section: Structural Variationmentioning

confidence: 99%

Disruption of regulatory domains and novel transcripts as disease‐causing mechanisms

Allou

Mundlos

2023

BioEssays

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“…The precision and the timing of such processes are pivotal for avoiding developmental defects or embryonic lethality, as an incorrect establishment of the embryonic epigenome would cause a defective zygotic genome activation (ZGA). Such a brief but crucial phase represents a window of vulnerability towards interfering maternal and environmental factors (such as chronic metabolic disorders, polycystic ovary syndrome, diet, and teratogen exposure), as highlighted by an ever-increasing number of studies [68][69][70][71]. In particular, it has been suggested that the association between assisted reproductive treatment (ART) procedures and slightly higher frequences of imprinting syndromes may be due to ART causing an abnormal epigenome in the offspring [71].…”

Section: Fertilization and Early Embryo Developmentmentioning

confidence: 99%

Epigenetics of pregnancy: looking beyond the DNA code

Zuccarello

Sorrentino

Brasson

et al. 2022

J Assist Reprod Genet

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Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal–fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders.

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“…In the model that we will refer to as the "condensates model", enhancers and promoters nucleate the formation of aggregates with high concentration of transcription factors. [57][58][59][60][61] This aggregate facilitates the assembly of transcriptional complexes in a local area and can produce a transcription burst at promoters within the condensate. [62] At some point, the condensate disperses and the transcription burst stops.…”

Section: Promoter-enhancer Contactsmentioning

confidence: 99%

Causality in transcription and genome folding: Insights from X inactivation

2022

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The spatial organization of genomes is becoming increasingly understood. In mammals, where it is most investigated, this organization ties in with transcription, so an important research objective is to understand whether gene activity is a cause or a consequence of genome folding in space. In this regard, the phenomena of X-chromosome inactivation and reactivation open a unique window of investigation because of the singularities of the inactive X chromosome. Here we focus on the cause-consequence nexus between genome conformation and transcription and explain how recent results about the structural changes associated with inactivation and reactivation of the X chromosome shed light on this problem.

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3D or Not 3D: Shaping the Genome during Development

Cited by 12 publications

References 132 publications

Disruption of regulatory domains and novel transcripts as disease‐causing mechanisms

Disruption of regulatory domains and novel transcripts as disease‐causing mechanisms

Epigenetics of pregnancy: looking beyond the DNA code

Causality in transcription and genome folding: Insights from X inactivation

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