Biology subjects

Perez-Cervantes, C.

Publications and source records attributed to Perez-Cervantes, C..

4 recordsLinked to original sources

bioRxiv2023

Tbx5 maintains atrial identity by regulating an atrial enhancer network

Understanding how the atrial and ventricular chambers of the heart maintain their distinct identity is a prerequisite for treating chamber-specific diseases. Here, we selectively inactivated the transcription factor Tbx5 in the atrial working myocardium of the neonatal mouse heart to show that it is required to maintain atrial identity. Atrial Tbx5 inactivation downregulated highly chamber specific genes such as Myl7 and Nppa, and conversely, increased the expression of ventricular identity genes including Myl2. Using combined single nucleus transcriptome and open chromatin profiling, we assessed genomic accessibility changes underlying the altered atrial identity expression program, identifying 1846 genomic loci with greater accessibility in control atrial cardiomyocytes compared to KO aCMs. 69% of the control-enriched ATAC regions were bound by TBX5, demonstrating a role for TBX5 in maintaining atrial genomic accessibility. These regions were associated with genes that had higher expression in control aCMs compared to KO aCMs, suggesting they act as TBX5-dependent enhancers. We tested this hypothesis by analyzing enhancer chromatin looping using HiChIP and found 510 chromatin loops that were sensitive to TBX5 dosage. Of the loops enriched in control aCMs, 73.7% contained anchors in control-enriched ATAC regions. Together, these data demonstrate a genomic role for TBX5 in maintaining the atrial gene expression program by binding to atrial enhancers and preserving tissue-specific chromatin architecture of atrial enhancers.

cell biology↗

bioRxiv2021

The cardiac lncRNA Chantico directly regulates Cxcl1 chemokine transcription

Withdrawal StatementThe corresponding author has withdrawn this preprint owing to inability to reproduce some of the data, instances of inappropriate data exclusion, and loss of much of the primary experimental records/data. Specifically, Figures 2B,E,H; 3; 4; 5A,B,D; 6; S2A,C; S4A; S5; and S6A,B and attendant text contain analyses for which the primary record and/or raw data no longer exist; the analyses, where still available, suffer from inappropriate data exclusion and thus should not be construed to be an accurate reflection of the experiments. Attempts by others in the lab to repeat several of the experiments in these indicated panels have failed reproduce the presented effects, despite showing much greater precision. Therefore the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

molecular biology↗

bioRxiv2019

Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types

Identification of the cis-regulatory elements (CREs) that regulate gene expression in specific cell types is critical for defining the gene regulatory networks (GRNs) that control normal physiology and disease states. We previously utilized non-coding RNA (ncRNA) profiling to define CREs that comprise a GRN in the adult mouse heart1. Here, we applied ncRNA profiling to the mouse retina in the presence and absence of Nrl, a rod photoreceptor-specific transcription factor required for rod versus cone photoreceptor cell fate. Differential expression of Nrl-dependent ncRNAs positively correlated with differential expression of Nrl-dependent local genes. Two distinct Nrl-dependent regulatory networks were discerned in parallel: Nrl-activated ncRNAs were enriched for accessible chromatin in rods but not cones whereas Nrl-repressed ncRNAs were enriched for accessible chromatin in cones but not rods. Furthermore, differential Nrl-dependent ncRNA expression levels quantitatively correlated with photoreceptor cell type-specific ATAC-seq read density. Direct assessment of Nrl-dependent ncRNA-defined loci identified functional cone photoreceptor CREs. This work supports differential ncRNA profiling as a platform for identifying context-specific regulatory elements and provides insight into the networks that define photoreceptor cell types.

molecular biology↗

bioRxiv2018

Hedgehog signaling controls progenitor differentiation timing during heart development

Heterochrony, defined as differences in the timing of developmental processes, impacts organ development, homeostasis, and regeneration. The molecular basis of heterochrony in mammalian tissues is poorly understood. We report that Hedgehog signaling activates a heterochronic pathway that controls differentiation timing in multiple lineages. A differentiation trajectory from second heart field cardiac progenitors to first heart field cardiomyocytes was identified by single-cell transcriptional profiling in mouse embryos. A survey of developmental signaling pathways revealed specific enrichment for Hedgehog signaling targets in cardiac progenitors. Removal of Hh signaling caused loss of progenitor and precocious cardiomyocyte differentiation gene expression in the second heart field in vivo. Introduction of active Hh signaling to mESC-derived progenitors, modelled by transient expression of the Hh-dependent transcription factor GLI1, delayed differentiation in cardiac and neural lineages in vitro. A shared GLI1-dependent network in both cardiac and neural progenitors was enriched with FOX family transcription factors. FOXF1, a GLI1 target, was sufficient to delay onset of the cardiomyocyte differentiation program in progenitors, by epigenetic repression of cardiomyocyte-specific enhancers. Removal of active Hh signaling or Foxf1 expression from second heart field progenitors caused precocious cardiac differentiation in vivo, establishing a mechanism for resultant Congenital Heart Disease. Together, these studies suggest that Hedgehog signaling directly activates a gene regulatory network that functions as a heterochronic switch to control differentiation timing across developmental lineages.

developmental biology↗