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The Interplay between 4D Genome, Transcription Factors, and Epigenetics in Transcriptional Regulation

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 12414

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Special Issue Editor

Dr. Petros Kolovos

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Guest Editor

Democritus University of Thrace, Department of Molecular Biology and Genetics, Alexandroupoli, Greece
Interests: Systems Biology; Chromatin Organization; Chromatin Conformation; Chromatin Structure; Chromatin architecture; Epigenetics; Transcription Factors; Transcription; CRISPR-Cas9; Hematopoiesis; Erythropoiesis; Gene regulation; Gene expression; Computational Biology

Special Issue Information

Dear Colleagues,

Recent technological advances, such as in the field of development and improvement of chromosome conformation capture techniques, as well as in the field of genomics, have strengthened our knowledge of 3D chromatin organization in various cell types, diseases, and organisms. Moreover, there is an increasing effort to unravel the 4D genome (the study of spatiotemporal 3D chromatin organization). At the same time, transcription factors and epigenetic mechanisms are known to play an important role in the control of gene expression. However, the interplay between 3D/4D chromatin architecture, transcription factors and epigenetics, and their combined effect in proper transcriptional regulation in developmental or differentiation processes, as well as in diseases, is still under heavy investigation.

Therefore, the aim of this Special Issue is to present recent advances (research articles, new or improved chromosome conformation capture techniques, and reviews) aiming to unveil the aforementioned interplay.

Dr. Petros Kolovos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

chromatin architecture
4D genome
transcription factors
epigenetics
transcriptional regulation
cell differentiation
development
diseases
chromosome conformation capture techniques, 3C, 4C, 5C, Hi-C
systems biology

Published Papers (6 papers)

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Research

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13 pages, 3085 KiB

Open AccessArticle

HMG20A Inhibit Adipogenesis by Transcriptional and Epigenetic Regulation of MEF2C Expression

by Ruixiao Li, Shan Meng, Mengting Ji, Xiaoyin Rong, Ziwei You, Chunbo Cai, Xiaohong Guo, Chang Lu, Guoming Liang, Guoqing Cao, Bugao Li and Yang Yang

Int. J. Mol. Sci. 2022, 23(18), 10559; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810559 - 12 Sep 2022

Cited by 5 | Viewed by 1474

Abstract

Obesity and its associated metabolic disease do serious harm to human health. The transcriptional cascade network with transcription factors as the core is the focus of current research on adipogenesis and its mechanism. Previous studies have found that HMG domain protein 20A (HMG20A) is highly expressed in the early stage of adipogenic differentiation of porcine intramuscular fat (IMF), which may be involved in regulating adipogenesis. In this study, HMG20A was found to play a key negative regulatory role in adipogenesis. Gain- and loss-of-function studies revealed that HMG20A inhibited the differentiation of SVF cells and C3H10T1/2 cells into mature adipocytes. RNA-seq was used to screen differentially expressed genes after HMG20A knockdown. qRT-PCR and ChIP-PCR confirmed that MEF2C was the real target of HMG20A, and HMG20A played a negative regulatory role through MEF2C. HMG20A binding protein LSD1 was found to alleviate the inhibitory effect of HMG20A on adipogenesis. Further studies showed that HMG20A could cooperate with LSD1 to increase the H3K4me2 of the MEF2C promoter and then increase the expression of MEF2C. Collectively, these findings highlight a role for HMG20A-dependent transcriptional and epigenetic regulation in adipogenesis. Full article

(This article belongs to the Special Issue The Interplay between 4D Genome, Transcription Factors, and Epigenetics in Transcriptional Regulation)

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16 pages, 2409 KiB

Open AccessArticle

Massive Loss of Transcription Factors Promotes the Initial Diversification of Placental Mammals

by Xin-Wei Zhao, Jiaqi Wu, Hirohisa Kishino and Ling Chen

Int. J. Mol. Sci. 2022, 23(17), 9720; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179720 - 26 Aug 2022

Cited by 1 | Viewed by 1551

Abstract

As one of the most successful group of organisms, mammals occupy a variety of niches on Earth as a result of macroevolution. Transcription factors (TFs), the fundamental regulators of gene expression, may also have evolved. To examine the relationship between TFs and mammalian macroevolution, we analyzed 140,821 de novo-identified TFs and their birth and death histories from 96 mammalian species. Gene tree vs. species tree reconciliation revealed that placental mammals experienced an upsurge in TF losses around 100 million years ago (Mya) and also near the Cretaceous–Paleogene boundary (K–Pg boundary, 66 Mya). Early Euarchontoglires, Laurasiatheria and marsupials appeared between 100 and 95 Mya and underwent initial diversification. The K-Pg boundary was associated with the massive extinction of dinosaurs, which lead to adaptive radiation of mammals. Surprisingly, TF loss decelerated, rather than accelerated, molecular evolutionary rates of their target genes. As the rate of molecular evolution is affected by the mutation rate, the proportion of neutral mutations and the population size, the decrease in molecular evolution may reflect increased functional constraints to survive target genes. Full article

(This article belongs to the Special Issue The Interplay between 4D Genome, Transcription Factors, and Epigenetics in Transcriptional Regulation)

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16 pages, 2216 KiB

Open AccessArticle

The Minus-End-Directed Kinesin OsDLK Shuttles to the Nucleus and Modulates the Expression of Cold-Box Factor 4

by Xiaolu Xu, Sabine Hummel, Klaus Harter, Üner Kolukisaoglu, Michael Riemann and Peter Nick

Int. J. Mol. Sci. 2022, 23(11), 6291; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116291 - 03 Jun 2022

Cited by 3 | Viewed by 1496

Abstract

The transition to terrestrial plants was accompanied by a progressive loss of microtubule minus-end-directed dynein motors. Instead, the minus-end-directed class-XIV kinesins expanded considerably, likely related to novel functions. One of these motors, OsDLK (Dual Localisation Kinesin from rice), decorates cortical microtubules but moves into the nucleus in response to cold stress. This analysis of loss-of-function mutants in rice indicates that OsDLK participates in cell elongation during development. Since OsDLK harbours both a nuclear localisation signal and a putative leucin zipper, we asked whether the cold-induced import of OsDLK into the nucleus might correlate with specific DNA binding. Conducting a DPI-ELISA screen with recombinant OsDLKT (lacking the motor domain), we identified the Opaque2 motif as the most promising candidate. This motif is present in the promoter of NtAvr9/Cf9, the tobacco homologue of Cold-Box Factor 4, a transcription factor involved in cold adaptation. A comparative study revealed that the cold-induced accumulation of NtAvr9/Cfp9 was specifically quelled in transgenic BY−2 cells overexpressing OsDLK-GFP. These findings are discussed as a working model, where, in response to cold stress, OsDLK partitions from cortical microtubules at the plasma membrane into the nucleus and specifically modulates the expression of genes involved in cold adaptation. Full article

(This article belongs to the Special Issue The Interplay between 4D Genome, Transcription Factors, and Epigenetics in Transcriptional Regulation)

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23 pages, 54342 KiB

Open AccessArticle

The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells

by Hongsen Liu, Tao Wei, Lin Sun, Tingting Wu, Fuqiang Li, Jianlei Zhao, Jinmeng Chu, Fei Wang, Yong Cai and Jingji Jin

Int. J. Mol. Sci. 2022, 23(7), 3801; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073801 - 30 Mar 2022

Cited by 2 | Viewed by 2092

Abstract

The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase (HAT) complex acetylates histone H4 at lysine K5, K8, and K16. This complex shares several subunits with other epigenetic regulatory enzymes, which highlights the complexity of its intracellular function. However, the effect of the NSL HAT complex on the genome and target genes in human cells is still unclear. By using a CRISPR/Cas9-mediated NSL3-knockout 293T cell line and chromatin immunoprecipitation-sequencing (ChIP-Seq) approaches, we identified more than 100 genes as NSL HAT transcriptional targets, including several transcription factors, such as Yin Yang 1 (YY1) which are mainly involved in cell proliferation, biological adhesion, and metabolic processes. We found here that the ChIP-Seq peaks of MOF and NSL3 co-localized with H4K16ac, H3K4me2, and H3K4me3 at the transcriptional start site of YY1. In addition, both the mRNA and protein expression levels of YY1 were regulated by silencing or overexpressing NSL HAT. Interestingly, the expression levels of cell division cycle 6, a downstream target gene of YY1, were regulated by MOF or NSL3. In addition, the suppressed clonogenic ability of HepG2 cells caused by siNSL3 was reversed by overexpressing YY1, suggesting the involvement of YY1 in NSL HAT functioning. Additionally, de novo motif analysis of MOF and NSL3 targets indicated that the NSL HAT complex may recognize the specific DNA-binding sites in the promoter region of target genes in order to regulate their transcription. Full article

(This article belongs to the Special Issue The Interplay between 4D Genome, Transcription Factors, and Epigenetics in Transcriptional Regulation)

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13 pages, 2118 KiB

Open AccessArticle

Identification and Functional Evaluation of a Novel TBX4 Mutation Underlies Small Patella Syndrome

by Ping Li, Wenli Lan, Jiaying Li, Yanping Zhang, Qiuhong Xiong, Jinpei Ye, Changxin Wu and Han Xiao

Int. J. Mol. Sci. 2022, 23(4), 2075; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042075 - 14 Feb 2022

Cited by 2 | Viewed by 1785

Abstract

Small patella syndrome (SPS) is a rare autosomal dominant disorder caused by mutations in TBX4 gene which encodes a transcription factor of FGF10. However, how TBX4 mutations result in SPS is poorly understood. Here, a novel TBX4 mutation c.1241C>T (p.P414L) was identified in a SPS family and series of studies were performed to evaluate the influences of TBX4 mutations (including c.1241C>T and two known mutations c.256G>C and c.743G>T). Results showed that mesenchymal stem cells (MSCs) with stable overexpression of either TBX4 wild-type (TBX4^wt) or mutants (TBX4^mt) were successfully generated. Immunofluorescence study revealed that both the overexpressed TBX4 wild-type and mutants were evenly expressed in the nucleus suggesting that these mutations do not alter the translocation of TBX4 into the nucleus. Interestingly, MSCs overexpression of TBX4^mt exhibited reduced differentiation activities and decreased FGF10 expression. Chromatin immunoprecipitation (ChIP) study demonstrated that TBX4 mutants still could bind to the promoter of FGF10. However, dual luciferase reporter assay clarified that the binding efficiencies of TBX4 mutants to FGF10 promoter were reduced. Taken together, MSCs were firstly used to study the function of TBX4 mutations in this study and the results indicate that the reduced binding efficiencies of TBX4 mutants (TBX4^mt) to the promoter of FGF10 result in the abnormal biological processes which provide important information for the pathogenesis of SPS. Full article

(This article belongs to the Special Issue The Interplay between 4D Genome, Transcription Factors, and Epigenetics in Transcriptional Regulation)

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Review

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13 pages, 901 KiB

Open AccessReview

Regulation of Gene Expression by Telomere Position Effect

by Kyung-Ha Lee, Do-Yeon Kim and Wanil Kim

Int. J. Mol. Sci. 2021, 22(23), 12807; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312807 - 26 Nov 2021

Cited by 7 | Viewed by 3082

Abstract

Many diseases that involve malignant tumors in the elderly affect the quality of human life; therefore, the relationship between aging and pathogenesis in geriatric diseases must be under-stood to develop appropriate treatments for these diseases. Recent reports have shown that epigenetic regulation caused by changes in the local chromatin structure plays an essential role in aging. This review provides an overview of the roles of telomere shortening on genomic structural changes during an age-dependent shift in gene expression. Telomere shortening is one of the most prominent events that is involved in cellular aging and it affects global gene expression through genome rearrangement. This review provides novel insights into the roles of telomere shortening in disease-affected cells during pathogenesis and suggests novel therapeutic approaches. Full article

(This article belongs to the Special Issue The Interplay between 4D Genome, Transcription Factors, and Epigenetics in Transcriptional Regulation)

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