Biology subjects

Roman, A. C.

Publications and source records attributed to Roman, A. C..

3 recordsLinked to original sources

bioRxiv2022

METTL3 regulates breast cancer-associated alternative splicing switches

Alternative splicing (AS) enables differential inclusion of exons from a given transcript, thereby contributing to the transcriptome and proteome diversity. Aberrant AS patterns play major roles in the development of different pathologies, including breast cancer. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, influences tumor progression and metastasis of breast cancer, and it has been recently linked to AS regulation. Here, we identify a specific AS signature associated with breast tumorigenesis in vitro. We characterize for the first time the role of METTL3 in modulating breast cancer-associated AS programs, expanding the role of the m6A-methyltransferase in tumorigenesis. Specifically, we find that both m6A deposition in splice site boundaries and in splicing and transcription factor transcripts, such as PHF5A and MYC, direct AS switches of specific breast cancer-associated transcripts. Finally, we show that five of the AS events validated in vitro are associated with a poor overall survival rate for patients with breast cancer, suggesting the use of these AS events as a novel potential prognostic biomarker.

cell biology↗

bioRxiv2021

ZFP207 controls pluripotency by multiple post-transcriptional mechanisms

The pluripotent state is not solely governed by the action of the core transcription factors Oct4, Sox2, and Nanog, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize the role of ZFP207 in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, ZFP207 does not transcriptionally regulate stem cell and neuronal-related genes but exerts its effects by control AS networks and acting as an RBP. Our study expands the role of ZFP207 to maintain ESC identity, and underscores ZFP207 functional versatility with key roles in neural fate commitment.

cell biology↗

bioRxiv2017

Histone 4 acetylation regulates behavioral individuality in zebrafish

Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We found that laboratory and isogenic zebrafish (Danio rerio) larvae showed consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. We also found that this behavioral inter-individual variability was reduced when we impaired the histone deacetylation pathway. Individuals with high levels of histone H4 acetylation, and specifically H4K12, behaved similar to the average of the population, but those with low levels deviated from it. More precisely, we found a set of genomic regions whose histone H4 acetylation is reduced with the distance between the individual and the average population behavior. We found evidence that this modulation depends on a complex of Yin-yang 1 (YY1) and histone deacetylase 1 (HDAC1) that binds to and deacetylates these regions. These changes were not only maintained at the transcriptional level but also amplified, as most target regions were located near genes encoding transcription factors. We suggest that stochasticity in the histone deacetylation pathway participates the generation of genetic-independent behavioral inter-individual variability.

animal behavior and cognition↗