Len A. Pennacchio

Large-scale discovery of neural enhancers for cis-regulation therapies

The paper identifies active human neural enhancers and CRISPRa gRNAs that upregulate NDD risk genes, providing a resource for cis-regulatory therapy development.

Uncovering Hidden Enhancers Through Unbiased In Vivo Testing

The paper identifies hidden enhancers in mouse embryos that are not detected by conventional chromatin profiling methods, highlighting a significant gap in enhancer discovery.

Conserved Cis-Acting Range Extender Element Mediates Extreme Long-Range Enhancer Activity in Mammals

The paper identifies a conserved cis-acting element, REX, that enables extreme long-range enhancer-promoter interactions in mammals by increasing the genomic interaction range of enhancers.

Mutagenesis Sensitivity Mapping of HumanEnhancers In Vivo

The paper maps the mutagenic sensitivity of human enhancers in vivo by systematically mutating enhancer sequences and using predictive modeling to identify critical nucleotides.

SOX2-VSX2 Co-Occupancy Shapes Retinal Neurogenesis Through Dynamic Chromatin Regulation

This study identifies SOX2 and VSX2 co-occupancy in retinal progenitor cells and shows how their cooperative binding regulates chromatin accessibility and neurogenesis.

Dissecting regulatory syntax in human development with scalable multiomics and deep learning

The paper presents a single-cell multi-omics atlas of human development and uses deep learning to analyze regulatory DNA motifs and their impact on chromatin accessibility and gene expression.

An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional Regulation

The paper expands the ENCODE Registry of candidate cis-regulatory elements (cCREs) to include 2.35 million human and 927 thousand mouse cCREs, revealing novel regulatory functions and identifying KLF1 as a causal gene for red blood cell traits.

ChromBPNet: bias factorized, base-resolution deep learning models of chromatin accessibility reveal cis-regulatory sequence syntax, transcription factor footprints and regulatory variants

Learning and removing Tn5/DNase-I sequence bias lets a small base-resolution CNN (ChromBPNet) recover TF motifs and footprints from accessibility data and rival Enformer at predicting chromatin QTL effects.

Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues

The paper maps chromatin interactions in mouse fetal tissues and links them to gene expression and disease risk variants in humans.

Interpreting variants associated with congenital heart disease with a regulatory map of the human fetal heart

This study creates a gene regulation map of the human fetal heart to interpret genetic variants associated with congenital heart disease and cardiac traits, identifying valvular interstitial cells as key regulators.

Combinatorial transcription factor binding encodes cis-regulatory wiring of forebrain GABAergic neurogenesis

The paper identifies combinatorial TF-cRE interactions in mouse basal ganglia development, revealing modules that drive GABAergic neurogenesis and suppress other fates.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders

The paper develops a cell type-aware framework to identify non-coding variants in Mendelian disorders by integrating single-cell multi-omic data and applying it to congenital cranial dysinnervation disorders.

Massively parallel reporter assays and mouse transgenic assays provide complementary information about neuronal enhancer activity

The paper combines massively parallel reporter assays and mouse transgenic assays to study the functional impact of non-coding variants on neuronal enhancer activity, finding strong correlations and additional pleiotropic effects.

Increased Enhancer-Promoter Interactions during Developmental Enhancer Activation in Mammals

The paper examines 3D enhancer-promoter interactions during mammalian development, finding that most enhancers bypass neighboring genes and show tissue-specific conformations with increased interactions upon activation.

Cell Type- and Tissue-specific Enhancers in Craniofacial Development

The paper identifies 14,000 human craniofacial enhancers across developmental stages and shows 56% are conserved in mice, providing cell type- and stage-specific activity profiles.

Single cell evaluation of endocardial HAND2 gene regulatory networks reveals critical HAND2 dependent pathways impacting cardiac morphogenesis.

The paper evaluates HAND2 gene regulatory networks in endocardial cells using single-cell transcriptomics to identify HAND2-dependent enhancers and their impact on cardiac morphogenesis.

Genome-Wide Fetalization of Enhancer Architecture in Heart Disease

The paper identifies widespread epigenomic changes in idiopathic dilated cardiomyopathy, showing a shift toward fetal-like enhancer states and providing a data resource for further study.

Single cell, whole embryo phenotyping of pleiotropic disorders of mammalian development

The paper uses single-cell RNA sequencing to systematically phenotype mouse genetic models, identifying molecular and cellular changes across multiple mutants and wildtypes.

Transcriptional Network Orchestrating Regional Patterning of Cortical Progenitors

The paper identifies a transcription factor network and enhancers involved in cortical regional patterning using mouse embryonic data.

Long-read metagenomics of soil communities reveals phylum-specific secondary metabolite dynamics

This study uses long-read metagenomics and metatranscriptomics to analyze soil communities, revealing phylum-specific secondary metabolite dynamics during wetting events.

De Novo Mutation in an Enhancer of EBF3 in simplex autism

Whole-genome sequencing in thousands of families reveals variants relevant to simplex autism in a brain enhancer of the well-established neurodevelopmental disorder gene EBF3.

Topologically Associating Domain Boundaries are Commonly Required for Normal Genome Function

This study shows that deleting TAD boundaries in mice often causes molecular or developmental phenotypes, highlighting their importance for genome function.

Deletion of a non-canonical regulatory sequence causes loss of Scn1a expression and epileptic phenotypes in mice

This study shows that deleting a non-canonical regulatory region of Scn1a in mice leads to reduced Scn1a expression and epileptic symptoms.

A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival

This study identifies a gene desert critical for Shox2 regulation and embryonic survival through enhancer networks in mouse development.

The changing mouse embryo transcriptome at whole tissue and single-cell resolution

The paper quantifies the mouse embryo transcriptome from E10.5 to birth using whole-tissue and single-cell RNA-seq, identifying key gene expression patterns and cell types.

Spatiotemporal DNA Methylome Dynamics of the Developing Mammalian Fetus

The paper maps DNA methylation changes across 12 mouse tissues at 8 developmental stages, identifying methylation variant regions and tissue-specific enhancers linked to human genetic diseases.

A cross-organism framework for supervised enhancer prediction with epigenetic pattern recognition and targeted validation

This paper develops a cross-organism framework for enhancer prediction using Drosophila STARR-seq data and supervised machine learning, validated in mouse and human with 153 enhancers.

Systematic mapping of chromatin state landscapes during mouse development

The paper systematically maps chromatin state landscapes during mouse development by profiling histone modifications across 72 tissue-stages, identifying dynamic enhancers and transcriptional regulators.

Parkinson-associated SNCA enhancer variants revealed by open chromatin in mouse dopamine neurons

The paper identifies Parkinson's risk variants in a SNCA enhancer by analyzing open chromatin in mouse dopamine neurons and validates their function in zebrafish and mice.

BAF chromatin remodeling complex subunit diversity promotes temporally distinct gene expression programs in cardiogenes

The paper identifies BAF complex subunit dynamics during cardiac differentiation, showing how BAF60c and BAF170 regulate gene expression programs in cardiac precursors and cardiomyocytes.