Polycomb and Trithorax factors in transcriptional and epigenetic regulation

Lau, Priscilla Nga Ieng; So, Chi Wai Eric

doi:10.1016/b978-0-12-799958-6.00004-4

Cited by 4 publications

(3 citation statements)

References 153 publications

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“…Homeotic transformations are well-studied phenomena found to occur due to mutations in Hox genes or dysregulation of chromatin regulating complexes. Trithorax group (TrxG) and Polycomb group (PcG) complexes are two opposing types of chromatin-modifiers that epigenetically regulate Hox gene expression ( Lau and So 2015 ). TrxG proteins promote target gene expression, while PcG proteins repress transcription through differential histone methylation.…”

Section: Discussionmentioning

confidence: 99%

Expression of human HIPKs in Drosophila demonstrates their shared and unique functions in a developmental model

Kinsey

Vinluan

Shipman

et al. 2021

G3 Genes|Genomes|Genetics

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Homeodomain-interacting protein kinases (HIPKs) are a family of four conserved proteins essential for vertebrate development, as demonstrated by defects in the eye, brain, and skeleton that culminate in embryonic lethality when multiple HIPKs are lost in mice. While HIPKs are essential for development, functional redundancy between the four vertebrate HIPK paralogues has made it difficult to compare their respective functions. Because understanding the unique and shared functions of these essential proteins could directly benefit the fields of biology and medicine, we addressed the gap in knowledge of the four vertebrate HIPK paralogues by studying them in the fruit fly Drosophila melanogaster, where reduced genetic redundancy simplifies our functional assessment. The single hipk present in the fly allowed us to perform rescue experiments with human HIPK genes that provide new insight into their individual functions not easily assessed in vertebrate models. Further, the abundance of genetic tools and established methods for monitoring specific developmental pathways and gross morphological changes in the fly allowed for functional comparisons in endogenous contexts. We first performed rescue experiments to demonstrate the extent to which each of the human HIPKs can functionally replace Drosophila Hipk for survival and morphological development. We then showed the ability of each human HIPK to modulate Armadillo/β-catenin levels, JAK/STAT activity, proliferation, growth, and death, each of which have previously been described for Hipks, but never all together in comparable tissue contexts. Finally, we characterized novel developmental phenotypes induced by human HIPKs to gain insight to their unique functions. Together, these experiments provide the first direct comparison of all four vertebrate HIPKs to determine their roles in a developmental context.

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Section: Discussionmentioning

confidence: 99%

Expression of human HIPKs in Drosophila demonstrates their shared and unique functions in a developmental model

Kinsey

Vinluan

Shipman

et al. 2021

G3 Genes|Genomes|Genetics

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“…Geminin interacts with members of the suppressive polycomb protein family as well as with the trithorax group of proteins that regulates neuronal development. The tuning in these network allows geminin to participate in the regulation of Hox genes among many others that controls the differentiation routes in progenitor cells (Kingston and Tamkun 2014;Lau and So 2015).…”

Section: Dna Damage Response In Stem Cellsmentioning

confidence: 99%

A Multilevel Approach to the Causes of Genetic Instability in Stem Cells

González

2022

Handbook of Stem Cell Therapy

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This chapter addresses the genetic instability in stem cells, a central feature that is an important determinant for the safety and effectiveness of cell-based therapies. First, DNA damage response mechanism and the gene network that regulates the DNA integrity homeostasis are revisited, focusing on relationship between genetic integrity and stemness maintenance. Also, several factors have been included that influence genetic instability in vivo, i.e., ROS generation and inflammation, and in vitro regarding cell isolation, culture conditions, i.e., oxygen levels and the use of feeder layers and different carriers, splitting procedures, passage number, etc. Telomere shortening, replicative senescence aneuploidy, and the senescence-associated secretory phenotype are different processes involved in deterioration of stem cells abilities for homing, reparability, and paracrine modulation. Moreover, less effective DNA repair upon senescence increases the propensity of developing tumors for stem cells that is one the main concerns related to genetic instability in stem cells. Nuclear organization and their determinants linked to chromosome aberrations and aneuploidy in stem cells and those epigenetic changes affecting stability are addressed. Differences between adipose, embryonic, and induced pluripotent stem cells are analyzed regarding to their ontogeny, changes in culture, and variation in proliferative capacity and stemness. The effect of reprogramming methods in genetic instability and variation in mutagenicity according to genes utilized for pluripotency induction, i.e., Yamanaka's factors and others, is discussed. Donor-related factors, i.e., age, smoking, and alcohol consumption, comorbidities, i.e., obesity, insulin resistance, diabetes, are mentioned for wide evaluation of genetic instability. The next years must witness consensus protocols that will contribute to control the effects of factors that alter stem cell genetic stability to increase the security and applicability of cell-based therapy.

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“…It has been a long-standing question how PRCs are recruited to their downstream targets in mammalian cells (Lau and So, 2015). This report proposes a collaborative combinatorial tethering mechanism mediated by EZH2/BCOR/BCL6 during GC B cell development, adding another level of complexity to the growing modes of PRC targeting (Klose et al, 2013).…”

mentioning

confidence: 94%