Features and mechanisms of canonical and noncanonical genomic imprinting [Reviews]
Genomic imprinting is the monoallelic expression of a gene based on parent of origin and is a consequence of differential epigenetic marking between the male and female germlines. Canonically, genomic imprinting is mediated by allelic DNA methylation. However, recently it has been shown that maternal H3K27me3 can result in DNA methylation-independent imprinting, termed "noncanonical imprinting." In this review, we compare and contrast what is currently known about the underlying mechanisms, the role of endogenous retroviral elements, and the conservation of canonical and noncanonical genomic imprinting. (Source: Genes and Development)
Source: Genes and Development - June 1, 2021 Category: Genetics & Stem Cells Authors: Hanna, C. W., Kelsey, G. Tags: Chromatin and Gene Expression Reviews Source Type: research
Genetic and biological hallmarks of colorectal cancer [Reviews]
Colorectal cancer has served as a genetic and biological paradigm for the evolution of solid tumors, and these insights have illuminated early detection, risk stratification, prevention, and treatment principles. Employing the hallmarks of cancer framework, we provide a conceptual framework to understand how genetic alterations in colorectal cancer drive cancer cell biology properties and shape the heterotypic interactions across cells in the tumor microenvironment. This review details research advances pertaining to the genetics and biology of colorectal cancer, emerging concepts gleaned from immune and single-cell profil...
Source: Genes and Development - June 1, 2021 Category: Genetics & Stem Cells Authors: Li, J., Ma, X., Chakravarti, D., Shalapour, S., DePinho, R. A. Tags: Cancer and Disease Models Reviews Source Type: research
Winter fields antisense RNAs to kick off flowering [Outlook]
FLOWERING LOCUS C (FLC), a MADS-box transcription factor, plays a major role in determining flowering time in Arabidopsis. In this issue of Genes & Development, Zhao and colleagues (pp. 888–898) elucidate the role of COOLAIR antisense noncoding RNAs in FLC regulation through field trials and laboratory experiments. COOLAIR-mediated FLC silencing is induced by the first seasonal frost in the field and thus acts as a key molecular indicator during autumn for winter arrival. (Source: Genes and Development)
Source: Genes and Development - June 1, 2021 Category: Genetics & Stem Cells Authors: Jin, Y., Marquardt, S. Tags: Plant Biology, Chromatin and Gene Expression Outlook Source Type: research
Corrigendum: FGF signaling regulates development by processes beyond canonical pathways [Errata]
(Source: Genes and Development)
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Ray, A. T., Mazot, P., Brewer, J. R., Catela, C., Dinsmore, C. J., Soriano, P. Tags: Errata Source Type: research
Corrigendum: H3.3 actively marks enhancers and primes gene transcription via opening higher-ordered chromatin [Errata]
(Source: Genes and Development)
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Chen, P., Zhao, J., Wang, Y., Wang, M., Long, H., Liang, D., Huang, L., Wen, Z., Li, W., Li, X., Feng, H., Zhao, H., Zhu, P., Li, M., Wang, Q.-f., Li, G. Tags: Errata Source Type: research
AGO HITS-CLIP reveals distinct miRNA regulation of white and brown adipose tissue identity [Resource/Methodology]
MicroRNAs (miRNAs) are short, noncoding RNAs that associate with Argonaute (AGO) to influence mRNA stability and translation, thereby regulating cellular determination and phenotype. While several individual miRNAs have been shown to control adipocyte function, including energy storage in white fat and energy dissipation in brown fat, a comprehensive analysis of miRNA activity in these tissues has not been performed. We used high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) to comprehensively characterize the network of high-confidence, in vivo mRNA:miRNA interactions across white ...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: O'Connor, S., Murphy, E. A., Szwed, S. K., Kanke, M., Marchildon, F., Sethupathy, P., Darnell, R. B., Cohen, P. Tags: Resource/Methodology Source Type: research
BAP1 constrains pervasive H2AK119ub1 to control the transcriptional potential of the genome [Research Papers]
Histone-modifying systems play fundamental roles in gene regulation and the development of multicellular organisms. Histone modifications that are enriched at gene regulatory elements have been heavily studied, but the function of modifications found more broadly throughout the genome remains poorly understood. This is exemplified by histone H2A monoubiquitylation (H2AK119ub1), which is enriched at Polycomb-repressed gene promoters but also covers the genome at lower levels. Here, using inducible genetic perturbations and quantitative genomics, we found that the BAP1 deubiquitylase plays an essential role in constraining H...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Fursova, N. A., Turberfield, A. H., Blackledge, N. P., Findlater, E. L., Lastuvkova, A., Huseyin, M. K., Dobrinic, P., Klose, R. J. Tags: Research Papers Source Type: research
Critical roles of transcriptional coactivator MED1 in the formation and function of mouse adipose tissues [Research Papers]
The MED1 subunit has been shown to mediate ligand-dependent binding of the Mediator coactivator complex to multiple nuclear receptors, including the adipogenic PPAR, and to play an essential role in ectopic PPAR-induced adipogenesis of mouse embryonic fibroblasts. However, the precise roles of MED1, and its various domains, at various stages of adipogenesis and in adipose tissue have been unclear. Here, after establishing requirements for MED1, including specific domains, for differentiation of 3T3L1 cells and both primary white and brown preadipocytes, we used multiple genetic approaches to assess requirements for MED1 in...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Ito, K., Schneeberger, M., Gerber, A., Jishage, M., Marchildon, F., Maganti, A. V., Cohen, P., Friedman, J. M., Roeder, R. G. Tags: Research Papers Source Type: research
MED1 is a lipogenesis coactivator required for postnatal adipose expansion [Research Papers]
MED1 often serves as a surrogate of the general transcription coactivator complex Mediator for identifying active enhancers. MED1 is required for phenotypic conversion of fibroblasts to adipocytes in vitro, but its role in adipose development and expansion in vivo has not been reported. Here, we show that MED1 is not generally required for transcription during adipogenesis in culture and that MED1 is dispensable for adipose development in mice. Instead, MED1 is required for postnatal adipose expansion and the induction of fatty acid and triglyceride synthesis genes after pups switch diet from high-fat maternal milk to carb...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Jang, Y., Park, Y.-K., Lee, J.-E., Wan, D., Tran, N., Gavrilova, O., Ge, K. Tags: Research Papers Source Type: research
Essential histone chaperones collaborate to regulate transcription and chromatin integrity [Research Papers]
In this study, we selected for suppressors of a temperature-sensitive spt6 mutation that disrupts the Spt6-Spn1 physical interaction and that also causes both transcription and chromatin defects. This selection identified novel mutations in FACT. Surprisingly, suppression by FACT did not restore the Spt6-Spn1 interaction, based on coimmunoprecipitation, ChIP, and mass spectrometry experiments. Furthermore, suppression by FACT bypassed the complete loss of Spn1. Interestingly, the FACT suppressor mutations cluster along the FACT-nucleosome interface, suggesting that they alter FACT-nucleosome interactions. In agreement with...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Viktorovskaya, O., Chuang, J., Jain, D., Reim, N. I., Lopez-Rivera, F., Murawska, M., Spatt, D., Churchman, L. S., Park, P. J., Winston, F. Tags: Research Papers Source Type: research
Meikin synergizes with shugoshin to protect cohesin Rec8 during meiosis I [Research Communications]
The conserved meiosis-specific kinetochore regulator, meikin (Moa1 in fission yeast) plays a central role in establishing meiosis-specific kinetochore function. However, the underlying molecular mechanisms remain elusive. Here, we show how Moa1 regulates centromeric cohesion protection, a function that has been previously attributed to shugoshin (Sgo1). Moa1 is known to associate with Plo1 kinase. We explore Plo1-dependent Rec8 phosphorylation and identify a key phosphorylation site required for cohesion protection. The phosphorylation of Rec8 by Moa1-Plo1 potentiates the activity of PP2A associated with Sgo1. This leads t...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Ma, W., Zhou, J., Chen, J., Carr, A. M., Watanabe, Y. Tags: Research Communications Source Type: research
Building a circuit through correlated spontaneous neuronal activity in the developing vertebrate and invertebrate visual systems [Reviews]
During the development of the vertebrate nervous systems, genetic programs assemble an immature circuit that is subsequently refined by neuronal activity evoked by external stimuli. However, prior to sensory experience, the intrinsic property of the developing nervous system also triggers correlated network-level neuronal activity, with retinal waves in the developing vertebrate retina being the best documented example. Spontaneous activity has also been found in the visual system of Drosophila. Here, we compare the spontaneous activity of the developing visual system between mammalian and Drosophila and suggest that Droso...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Choi, B. J., Chen, Y.-C. D., Desplan, C. Tags: Neurobiology Reviews Source Type: research
Protein phosphatases in the RNAPII transcription cycle: erasers, sculptors, gatekeepers, and potential drug targets [Reviews]
The transcription cycle of RNA polymerase II (RNAPII) is governed at multiple points by opposing actions of cyclin-dependent kinases (CDKs) and protein phosphatases, in a process with similarities to the cell division cycle. While important roles of the kinases have been established, phosphatases have emerged more slowly as key players in transcription, and large gaps remain in understanding of their precise functions and targets. Much of the earlier work focused on the roles and regulation of sui generis and often atypical phosphatases—FCP1, Rtr1/RPAP2, and SSU72—with seemingly dedicated functions in RNAPII tr...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Cossa, G., Parua, P. K., Eilers, M., Fisher, R. P. Tags: Reviews Source Type: research
Hepatic transcriptional responses to fasting and feeding [Reviews]
Mammals undergo regular cycles of fasting and feeding that engage dynamic transcriptional responses in metabolic tissues. Here we review advances in our understanding of the gene regulatory networks that contribute to hepatic responses to fasting and feeding. The advent of sequencing and -omics techniques have begun to facilitate a holistic understanding of the transcriptional landscape and its plasticity. We highlight transcription factors, their cofactors, and the pathways that they impact. We also discuss physiological factors that impinge on these responses, including circadian rhythms and sex differences. Finally, we ...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Bideyan, L., Nagari, R., Tontonoz, P. Tags: Molecular Physiology and Metabolism, Chromatin and Gene Expression Reviews Source Type: research
Establishing and maintaining fertility: the importance of cell cycle arrest [Reviews]
Development of the ovary or testis is required to establish reproductive competence. Gonad development relies on key cell fate decisions that occur early in embryonic development and are actively maintained. During gonad development, both germ cells and somatic cells proliferate extensively, a process facilitated by cell cycle regulation. This review focuses on the Cip/Kip family of cyclin-dependent kinase inhibitors (CKIs) in mouse gonad development. We particularly highlight recent single-cell RNA sequencing studies that show the heterogeneity of cyclin-dependent kinase inhibitors. This diversity highlights new roles for...
Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Frost, E. R., Taylor, G., Baker, M. A., Lovell-Badge, R., Sutherland, J. M. Tags: Cell Cycle and DNA Replication Reviews Source Type: research
