Q-rich activation domains: flexible 'rulers' for transcription start site selection?

Recent findings broadened the function of RNA polymerase II (Pol II) proximal promoter motifs from quantitative regulators of transcription to important determinants of transcription start site (TSS) position. These motifs are recognized by transcription factors (TFs) that we propose to term 'ruler' TFs (rTFs), such as NRF1, NF-Y, YY1, ZNF143, BANP, and members of the SP, ETS, and CRE families, sharing as a common feature a glutamine-rich (Q-rich) effector domain also enriched in valine, isoleucine, and threonine (QVIT-rich). We propose that rTFs guide TSS location by constraining the position of the pre-initiation complex (PIC) during its promoter recognition phase through a specialized, and still enigmatic, class of activation domains.

The role(s) of NF-Y in development and differentiation.

NF-Y is a conserved sequence-specific trimeric Transcription Factor -TF- binding to the CCAAT element. We review here the role(s) in development, from pre-implantation embryo to terminally differentiated tissues, by rationalizing and commenting on genetic, genomic, epigenetic and biochemical studies. This effort brings to light the impact of NF-YA isoforms on stemness and differentiation, as well as binding to distal vs promoter proximal sites and connections with selected TFs.

Genomic binding of NF-Y in mouse and human cells.

NF-Y is a Transcription Factor that regulates transcription through binding to the CCAAT-box. To understand its strategy, we analyzed 16 ChIP-seq datasets from human and mouse cells. Shared loci, mostly located in promoters of expressed genes of cell cycle, metabolism and gene expression pathways, are associated with histone marks of active chromatin and specific modules of TFs.

A first characterization of the microbiota-resilience link in swine.

Background: The gut microbiome plays a crucial role in understanding complex biological mechanisms, including host resilience to stressors. Investigating the microbiota-resilience link in animals and plants holds relevance in addressing challenges like adaptation of agricultural species to a warming environment. This study aims to characterize the microbiota-resilience connection in swine.

Expression and function of NF-Y subunits in cancer.

NF-Y is a Transcription Factor (TF) targeting the CCAAT box regulatory element. It consists of the NF-YB/NF-YC heterodimer, each containing an Histone Fold Domain (HFD), and the sequence-specific subunit NF-YA. NF-YA expression is associated with cell proliferation and absent in some post-mitotic cells.

Genetic correlations of direct and indirect genetic components of social dominance with fitness and morphology traits in cattle.

Background: Within the same species, individuals show marked variation in their social dominance. Studies on a handful of populations have indicated heritable genetic variation for this trait, which is determined by both the genetic background of the individual (direct genetic effect) and of its opponent (indirect genetic effect). However, the evolutionary consequences of selection for this trait are largely speculative, as it is not a usual target of selection in livestock populations.

Myo-differentiation reporter screen reveals NF-Y as an activator of PAX3-FOXO1 in rhabdomyosarcoma.

Recurrent chromosomal rearrangements found in rhabdomyosarcoma (RMS) produce the PAX3-FOXO1 fusion protein, which is an oncogenic driver and a dependency in this disease. One important function of PAX3-FOXO1 is to arrest myogenic differentiation, which is linked to the ability of RMS cells to gain an unlimited proliferation potential. Here, we developed a phenotypic screening strategy for identifying factors that collaborate with PAX3-FOXO1 to block myo-differentiation in RMS.

Long-Term SARS-CoV-2 Antibody Seroprevalence in Blood Donors, Italy.

We evaluated SARS-CoV-2 antibody response in voluntary blood donors in Italy at different timepoints. Immediately after lockdown easing, 908/25,657 donors (3.5%) had low IgG titers against nucleocapsid.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

Exploring the Italian equine gene pool high-throughput genotyping.

The Italian peninsula is in the center of the Mediterranean area, and historically it has been a hub for numerous human populations, cultures, and also animal species that enriched the hosted biodiversity. Horses are no exception to this phenomenon, with the peculiarity that the gene pool has been impacted by warfare and subsequent "colonization". In this study, using a comprehensive dataset for almost the entire Italian equine population, in addition to the most influential cosmopolitan breeds, we describe the current status of the modern Italian gene pool.

NF-YAl drives EMT in Claudin tumours.

NF-Y is a trimeric transcription factor whose binding site -the CCAAT box- is enriched in cancer-promoting genes. The regulatory subunit, the sequence-specificity conferring NF-YA, comes in two major isoforms, NF-YA long (NF-YAl) and short (NF-YAs). Extensive expression analysis in epithelial cancers determined two features: widespread overexpression and changes in NF-YAl/NF-YAs ratios (NF-YAr) in tumours with EMT features.

Improvement of Genomic Predictions in Small Breeds by Construction of Genomic Relationship Matrix Through Variable Selection.

Genomic selection has been increasingly implemented in the animal breeding industry, and it is becoming a routine method in many livestock breeding contexts. However, its use is still limited in several small-population local breeds, which are, nonetheless, an important source of genetic variability of great economic value. A major roadblock for their genomic selection is accuracy when population size is limited: to improve breeding value accuracy, variable selection models that assume heterogenous variance have been proposed over the last few years.

Phylogeny of NF-YA trans-activation splicing isoforms in vertebrate evolution.

NF-Y is a trimeric pioneer Transcription Factor (TF) whose target sequence -the CCAAT box- is present in ~25% of mammalian promoters. We reconstruct the phylogenetic history of the regulatory NF-YA subunit in vertebrates. We find that in addition to the remarkable conservation of the subunits-interaction and DNA-binding parts, the Transcriptional Activation Domain (TAD) is also conserved (>90% identity among bony vertebrates).

Genotype by Environment Interaction and Selection Response for Milk Yield Traits and Conformation in a Local Cattle Breed Using a Reaction Norm Approach.

Local breeds are often reared in various environmental conditions (EC), suggesting that genotype by environment interaction (GxE) could influence genetic progress. This study aimed at investigating GxE and response to selection (R) in Rendena cattle under diverse EC. Traits included milk, fat, and protein yields, fat and protein percentage, and somatic cell score, three-factor scores and 24 linear type traits.

Comparative analysis of inbreeding parameters and runs of homozygosity islands in 2 Italian autochthonous cattle breeds mainly raised in the Parmigiano-Reggiano cheese production region.

Reggiana and Modenese are autochthonous cattle breeds, reared in the North of Italy, that can be mainly distinguished for their standard coat color (Reggiana is red, whereas Modenese is white with some pale gray shades). Almost all milk produced by these breeds is transformed into 2 mono-breed branded Parmigiano-Reggiano cheeses, from which farmers receive the economic incomes needed for the sustainable conservation of these animal genetic resources. After the setting up of their herd books in 1960s, these breeds experienced a strong reduction in the population size that was subsequently reverted starting in the 1990s (Reggiana) or more recently (Modenese) reaching at present a total of about 2,800 and 500 registered cows, respectively.

NF-Y subunits overexpression in gastric adenocarcinomas (STAD).

NF-Y is a pioneer transcription factor-TF-formed by the Histone-like NF-YB/NF-YC subunits and the regulatory NF-YA. It binds to the CCAAT box, an element enriched in promoters of genes overexpressed in many types of cancer. NF-YA is present in two major isoforms-NF-YAs and NF-YAl-due to alternative splicing, overexpressed in epithelial tumors.

The USR domain of USF1 mediates NF-Y interactions and cooperative DNA binding.

The trimeric CCAAT-binding NF-Y is a "pioneer" Transcription Factor -TF- known to cooperate with neighboring TFs to regulate gene expression. Genome-wide analyses detected a precise stereo-alignment -10/12 bp- of CCAAT with E-box elements and corresponding colocalization of NF-Y with basic-Helix-Loop-Helix (bHLH) TFs. We dissected here NF-Y interactions with USF1 and MAX.

The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle.

The transcription factor NF-Y promotes cell proliferation and its activity often declines during differentiation through the regulation of NF-YA, the DNA binding subunit of the complex. In stem cell compartments, the shorter NF-YA splice variant is abundantly expressed and sustains their expansion. Here, we report that satellite cells, the stem cell population of adult skeletal muscle necessary for its growth and regeneration, express uniquely the longer NF-YA isoform, majorly associated with cell differentiation.

NF-Y Subunits Overexpression in HNSCC.

NF-Y is the CCAAT-binding trimer formed by the histone fold domain (HFD), NF-YB/NF-YC and NF-YA. The CCAAT box is generally prevalent in promoters of "cancer" genes. We reported the overexpression of NF-YA in BRCA, LUAD and LUSC, and of all subunits in HCC.

Genomic Prediction in Local Breeds: The Rendena Cattle as a Case Study.

The maintenance of local cattle breeds is key to selecting for efficient food production, landscape protection, and conservation of biodiversity and local cultural heritage. Rendena is an indigenous cattle breed from the alpine North-East of Italy, selected for dual purpose, but with lesser emphasis given to beef traits. In this situation, increasing accuracy for beef traits could prevent detrimental effects due to the antagonism with milk production.

High Conformational Flexibility of the E2F1/DP1/DNA Complex.

The E2F1 transcription factor is a master regulator of cell-cycle progression whose uncontrolled activation contributes to tumor cells growth. E2F1 binds DNA as a heterodimer with DP partners, resulting in a multi-domain quaternary-structure complex composed of DNA binding domains, a coiled coil domain and a marked box domain separated by short linkers. Building on the 3D knowledge of the single domains of E2F and DPs, we characterized the structure and dynamics of the complete E2F1/DP1/DNA complex by a combination of small-angle X-ray scattering and molecular dynamics simulations.

Selection Response Due to Different Combination of Antagonistic Milk, Beef, and Morphological Traits in the Alpine Grey Cattle Breed.

Selection in local dual-purpose breeds requires great carefulness because of the need to preserve peculiar traits and also guarantee the positive genetic progress for milk and beef production to maintain economic competitiveness. A specific breeding plan accounting for milk, beef, and functional traits is required by breeders of the Alpine Grey cattle (AG), a local dual-purpose breed of the Italian Alps. Hereditability and genetic correlations among all traits have been analyzed for this purpose.