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Transcriptional Regulation of Early Embryogenesis

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 35509

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Special Issue Editor

Prof. Dr. Daniel Weinstein

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Guest Editor

Department of Biology, Queens College, City University of New York, Flushing, CA 10016, USA
Interests: developmental biology; germ layer formation; Xenopus; gene expression; cell signaling

Special Issue Information

Dear colleagues,

A fundamental focus of developmental biology is the process by which the single cell of the fertilized egg gives rise to the many cell types within a multicellular organism. Differential gene expression among genetically equivalent cells, often regulated at the initiating step of transcription, underlies the emergence and maintenance of distinct fates during embryogenesis. Precise spatial and temporal control of transcription is thus essential for normal development.

This Special Issue will highlight recent advances in our understanding of the transcriptional regulation of animal development. Particular emphasis will be given to the genetic and epigenetic mechanisms that influence cellular pluripotency, competence, and cell fate suppression during vertebrate embryogenesis. We welcome the submission of reviews, perspectives, short communications, and research articles.

Prof. Daniel Weinstein
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. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

Development
Gene expression
Pluripotency
Epigenetics
Transcriptional regulation

Published Papers (6 papers)

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Research

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16 pages, 2353 KiB

Open AccessArticle

The H3K9 Methylation Writer SETDB1 and its Reader MPP8 Cooperate to Silence Satellite DNA Repeats in Mouse Embryonic Stem Cells

by Paola Cruz-Tapias, Philippe Robin, Julien Pontis, Laurence Del Maestro and Slimane Ait-Si-Ali

Genes 2019, 10(10), 750; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100750 - 25 Sep 2019

Cited by 13 | Viewed by 4447

Abstract

SETDB1 (SET Domain Bifurcated histone lysine methyltransferase 1) is a key lysine methyltransferase (KMT) required in embryonic stem cells (ESCs), where it silences transposable elements and DNA repeats via histone H3 lysine 9 tri-methylation (H3K9me3), independently of DNA methylation. The H3K9 methylation reader M-Phase Phosphoprotein 8 (MPP8) is highly expressed in ESCs and germline cells. Although evidence of a cooperation between H3K9 KMTs and MPP8 in committed cells has emerged, the interplay between H3K9 methylation writers and MPP8 in ESCs remains elusive. Here, we show that MPP8 interacts physically and functionally with SETDB1 in ESCs. Indeed, combining biochemical, transcriptomic and genomic analyses, we found that MPP8 and SETDB1 co-regulate a significant number of common genomic targets, especially the DNA satellite repeats. Together, our data point to a model in which the silencing of a class of repeated sequences in ESCs involves the cooperation between the H3K9 methylation writer SETDB1 and its reader MPP8. Full article

(This article belongs to the Special Issue Transcriptional Regulation of Early Embryogenesis)

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17 pages, 4607 KiB

Open AccessArticle

HNF4A Regulates the Formation of Hepatic Progenitor Cells from Human iPSC-Derived Endoderm by Facilitating Efficient Recruitment of RNA Pol II

by Ann DeLaForest, Francesca Di Furio, Ran Jing, Amy Ludwig-Kubinski, Kirk Twaroski, Amanda Urick, Kirthi Pulakanti, Sridhar Rao and Stephen A. Duncan

Genes 2019, 10(1), 21; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10010021 - 28 Dec 2018

Cited by 25 | Viewed by 5131

Abstract

Elucidating the molecular basis of cell differentiation will advance our understanding of organ development and disease. We have previously established a protocol that efficiently produces cells with hepatocyte characteristics from human induced pluripotent stem cells. We previously used this cell differentiation model to identify the transcription factor hepatocyte nuclear factor 4 α (HNF4A) as being essential during the transition of the endoderm to a hepatic fate. Here, we sought to define the molecular mechanisms through which HNF4A controls this process. By combining HNF4A chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) analyses at the onset of hepatic progenitor cell formation with transcriptome data collected during early stages of differentiation, we identified genes whose expression is directly dependent upon HNF4A. By examining the dynamic changes that occur at the promoters of these HNF4A targets we reveal that HNF4A is essential for recruitment of RNA polymerase (RNA pol) II to genes that are characteristically expressed as the hepatic progenitors differentiate from the endoderm. Full article

(This article belongs to the Special Issue Transcriptional Regulation of Early Embryogenesis)

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Review

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16 pages, 1213 KiB

Open AccessReview

Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation

by Kimiko Takebayashi-Suzuki and Atsushi Suzuki

Genes 2020, 11(3), 341; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11030341 - 24 Mar 2020

Cited by 9 | Viewed by 5336

Abstract

During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family control the dorsal–ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior–posterior (AP) axis. Activation of morphogen signaling results in changes in the expression of target genes including transcription factors that direct cell fate along the body axes. To ensure the correct establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated by a fine-tuning of morphogen signaling. In this review, we focus on the interplay of various intracellular regulatory mechanisms and discuss how communication among morphogen signaling pathways modulates body axis formation in vertebrate embryos. Full article

(This article belongs to the Special Issue Transcriptional Regulation of Early Embryogenesis)

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33 pages, 2615 KiB

Open AccessReview

Evolving Role of RING1 and YY1 Binding Protein in the Regulation of Germ-Cell-Specific Transcription

by Izabella Bajusz, Surya Henry, Enikő Sutus, Gergő Kovács and Melinda K. Pirity

Genes 2019, 10(11), 941; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10110941 - 19 Nov 2019

Cited by 11 | Viewed by 4999

Abstract

Separation of germline cells from somatic lineages is one of the earliest decisions of embryogenesis. Genes expressed in germline cells include apoptotic and meiotic factors, which are not transcribed in the soma normally, but a number of testis-specific genes are active in numerous cancer types. During germ cell development, germ-cell-specific genes can be regulated by specific transcription factors, retinoic acid signaling and multimeric protein complexes. Non-canonical polycomb repressive complexes, like ncPRC1.6, play a critical role in the regulation of the activity of germ-cell-specific genes. RING1 and YY1 binding protein (RYBP) is one of the core members of the ncPRC1.6. Surprisingly, the role of Rybp in germ cell differentiation has not been defined yet. This review is focusing on the possible role of Rybp in this process. By analyzing whole-genome transcriptome alterations of the Rybp^-/- embryonic stem (ES) cells and correlating this data with experimentally identified binding sites of ncPRC1.6 subunits and retinoic acid receptors in ES cells, we propose a model how germ-cell-specific transcription can be governed by an RYBP centered regulatory network, underlining the possible role of RYBP in germ cell differentiation and tumorigenesis. Full article

(This article belongs to the Special Issue Transcriptional Regulation of Early Embryogenesis)

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14 pages, 2150 KiB

Open AccessReview

Repression of Inappropriate Gene Expression in the Vertebrate Embryonic Ectoderm

by Shoshana Reich and Daniel C. Weinstein

Genes 2019, 10(11), 895; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10110895 - 06 Nov 2019

Cited by 3 | Viewed by 4552

Abstract

During vertebrate embryogenesis, precise regulation of gene expression is crucial for proper cell fate determination. Much of what we know about vertebrate development has been gleaned from experiments performed on embryos of the amphibian Xenopus laevis; this review will focus primarily on studies of this model organism. An early critical step during vertebrate development is the formation of the three primary germ layers—ectoderm, mesoderm, and endoderm—which emerge during the process of gastrulation. While much attention has been focused on the induction of mesoderm and endoderm, it has become clear that differentiation of the ectoderm involves more than the simple absence of inductive cues; rather, it additionally requires the inhibition of mesendoderm-promoting genes. This review aims to summarize our current understanding of the various inhibitors of inappropriate gene expression in the presumptive ectoderm. Full article

(This article belongs to the Special Issue Transcriptional Regulation of Early Embryogenesis)

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22 pages, 2367 KiB

Open AccessReview

The Role of Insulation in Patterning Gene Expression

by Isa Özdemir and Maria Cristina Gambetta

Genes 2019, 10(10), 767; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100767 - 28 Sep 2019

Cited by 24 | Viewed by 10521

Abstract

Development is orchestrated by regulatory elements that turn genes ON or OFF in precise spatial and temporal patterns. Many safety mechanisms prevent inappropriate action of a regulatory element on the wrong gene promoter. In flies and mammals, dedicated DNA elements (insulators) recruit protein factors (insulator binding proteins, or IBPs) to shield promoters from regulatory elements. In mammals, a single IBP called CCCTC-binding factor (CTCF) is known, whereas genetic and biochemical analyses in Drosophila have identified a larger repertoire of IBPs. How insulators function at the molecular level is not fully understood, but it is currently thought that they fold chromosomes into conformations that affect regulatory element-promoter communication. Here, we review the discovery of insulators and describe their properties. We discuss recent genetic studies in flies and mice to address the question: Is gene insulation important for animal development? Comparing and contrasting observations in these two species reveal that they have different requirements for insulation, but that insulation is a conserved and critical gene regulation strategy. Full article

(This article belongs to the Special Issue Transcriptional Regulation of Early Embryogenesis)

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