Introduction to Genome Biology and Diversity

Youssef, Noor; Budd, Aidan; Bielawski, Joseph P.

doi:10.1007/978-1-4939-9074-0_1

Cited by 10 publications

(7 citation statements)

References 168 publications

(193 reference statements)

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“…However, it is unclear how these mitogens are initially induced in the epicardium. Epigenetics has been increasingly recognized as an important regulator of gene transcription in a variety of phycological/pathological processes including cardiac development and congenital diseases 62, 63 . Our current study suggests that HDAC3 induces the expression of FGF9 and IGF2 in the epicardium, and thus stimulates ventricular myocardial wall expansion through paracrine signaling.…”

Section: Discussionmentioning

confidence: 99%

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

Jang

Song

et al. 2021

Preprint

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Rational: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells (EPDCs) instruct myocardial growth by secreting essential factors including fibroblast growth factor 9 (FGF9) and insulin-like growth factor 2 (IGF2). However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. Objective: To understand whether and how histone deacetylase 3 (HDAC3) in the developing epicardium regulates myocardial growth. Methods and Results: We deleted Hdac3 in the developing murine epicardium and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of EPDCs. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells (MECs) also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly down-regulated in Hdac3 KO MECs. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO MECs and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO MECs. Conclusions: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322/miR-503, providing novel insights in elucidating etiology of congenital heart defects, and conceptual strategies to promote myocardial regeneration.

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Section: Discussionmentioning

confidence: 99%

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

Jang

Song

et al. 2021

Preprint

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“…These repeats are further classified into two subcategories: (A) microsatellites and minisatellites (VNTR), and (B) dispersed repeats, which are primarily made up of transposable elements ( TEs ) 20 . It is worth noting that many moderate-frequency repeats have been implicated in gene expression regulation 21 .…”

Section: Introductionmentioning

confidence: 99%

Repetitive DNA sequence detection and its role in the human genome

Liao,

Zhu,

Zhou

et al. 2023

Commun Biol

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Repetitive DNA sequences playing critical roles in driving evolution, inducing variation, and regulating gene expression. In this review, we summarized the definition, arrangement, and structural characteristics of repeats. Besides, we introduced diverse biological functions of repeats and reviewed existing methods for automatic repeat detection, classification, and masking. Finally, we analyzed the type, structure, and regulation of repeats in the human genome and their role in the induction of complex diseases. We believe that this review will facilitate a comprehensive understanding of repeats and provide guidance for repeat annotation and in-depth exploration of its association with human diseases.

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“…The mechanisms of transcriptional regulation are very different in prokaryotes and eukaryotes, and are generally more complex in the latter. For example, in eukaryotes the genomes are packed in more sophisticated ways and transcriptional regulators rely less on sequence specificity for DNA response elements (REs; Youssef et al, 2019). The reason for this higher level of sophistication is most likely related with intercellular communication in multicellular organisms, which becomes clear when considering situations in which gene regulation is disturbed and causes disease (Lee & Young, 2013).…”

Section: Introductionmentioning

confidence: 99%

A tetramerization domain in prokaryotic and eukaryotic transcription regulators homologous to p53

Bernardo¹,

Cuppari²,

Meijer³

et al. 2023

Acta Crystallogr D Struct Biol

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Transcriptional regulation usually requires the action of several proteins that either repress or activate a promotor of an open reading frame. These proteins can counteract each other, thus allowing tight regulation of the transcription of the corresponding genes, where tight repression is often linked to DNA looping or cross-linking. Here, the tetramerization domain of the bacterial gene repressor Rco from Bacillus subtilis plasmid pLS20 (RcopLS20) has been identified and its structure is shown to share high similarity to the tetramerization domain of the well known p53 family of human tumor suppressors, despite lacking clear sequence homology. In RcopLS20, this tetramerization domain is responsible for inducing DNA looping, a process that involves multiple tetramers. In accordance, it is shown that RcopLS20 can form octamers. This domain was named TetDloop and its occurrence was identified in other Bacillus species. The TetDloop fold was also found in the structure of a transcriptional repressor from Salmonella phage SPC32H. It is proposed that the TetDloop fold has evolved through divergent evolution and that the TetDloop originates from a common ancestor predating the occurrence of multicellular life.

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Introduction to Genome Biology and Diversity

Cited by 10 publications

References 168 publications

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

Repetitive DNA sequence detection and its role in the human genome

A tetramerization domain in prokaryotic and eukaryotic transcription regulators homologous to p53

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