Foundational

Intermediate

Advanced

Reference & case studies

Explain it to me like I'm…High-school biology — proper terms explained

Genetics news

Curated headlines in genetics with source links and level-matched explanations of the science behind each report.

Curated genetics headlines with links to original reporting. Each item explains the science behind the news at your chosen depth.

SourceA genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cellsJul 1, 2026 · Nature Biotechnology

CRISPRFunctional genomicsStem cells

CRISPR interference: silencing without cutting

CRISPR interference (CRISPRi) uses a modified, "dead" version of the Cas9 protein that can still find and bind a target gene using a guide RNA, but no longer cuts DNA. It is fused to a repressor piece that blocks the gene from being read, temporarily lowering its activity rather than deleting it.

The researchers used CRISPRi to individually silence 11,692 expressed genes in induced pluripotent stem cells (iPSCs), human cells reprogrammed from adult tissue that can be coaxed into becoming almost any cell type in the body.

Perturb-seq: linking each silenced gene to its effect

The method, called Perturb-seq, combines CRISPRi with single-cell RNA sequencing: each cell’s guide RNA is sequenced alongside its transcriptome, linking "which gene was silenced" to "what changed" in that same cell. Across more than 2.5 million single cells, this produced a transcriptional signature for each of the 11,692 targeted genes.

Genes whose knockdown produced correlated transcriptional signatures were grouped together, recreating known protein complexes (groups of proteins that physically work together) purely from how similar their silencing effects looked at the RNA level.

New pluripotency genes and a bonus RNA-editing screen

Two previously uncharacterised genes stood out: ZBTB41, linked to metabolic regulation, and RNF7, a regulator of the pluripotent state. The authors confirmed their roles using independent methods, including metabolic tracing, immunofluorescence imaging, and assays that detect direct protein–protein interactions, rather than relying on the screen alone.

The same dataset was also mined for regulators of A-to-I RNA editing, a process where an enzyme chemically converts one RNA letter into another after a gene is transcribed. This secondary analysis identified DBR1 as a strong modulator of editing levels, a gene not previously linked to this process.

Key takeaways

CRISPRi uses dead Cas9 plus a repressor to silence genes without cutting DNA.
Perturb-seq links each silenced gene to its single-cell transcriptional effect across 11,692 genes.
Newly validated genes ZBTB41 (metabolism) and RNF7 (pluripotency), plus DBR1 as an RNA-editing regulator.

Curated genetics headlines with links to original reporting. Each item explains the science behind the news at your chosen depth.

SourceSingle-cell four-omics with CHARMJun 12, 2026 · Nature Reviews Genetics

Single-cellMulti-omicsEpigenomics

The problem with measuring genome layers separately

A cell’s genome is organised on several linked levels: its 3D folding pattern (genome conformation), which stretches are physically open for proteins to access (chromatin accessibility), chemical flags on the DNA-packaging proteins (histone modifications), and which genes are actively being copied into RNA (gene expression). These levels influence each other, but most methods can only measure one or two at a time, and usually from separate pools of cells.

That is a problem in tissues where cells differ in type, state, or stage of a process like the cell cycle: averaging across many different cells blurs exactly the relationships researchers want to see. CHARM instead measures all four layers from the same individual cell.

How CHARM tells the four signals apart

CHARM uses a transposase, an enzyme that cuts and inserts short DNA sequences, to attach a distinct molecular tag to fragments from each modality before they are pooled and processed together as one "one-pot" reaction, rather than being physically separated during the experiment.

After sequencing, software reads each tag to assign every DNA or RNA fragment back to its correct modality (conformation, accessibility, a histone mark, or expression). This simplifies the lab workflow while still letting researchers computationally reconstruct four separate readouts from a single nucleus.

Key takeaways

CHARM jointly profiles genome conformation, chromatin accessibility, selected histone modifications (e.g. H3K27me3), and gene expression in one nucleus.
A transposase-based tagging strategy lets all four assays run in a single "one-pot" reaction.
It builds on the earlier HiRES method, which combined single-cell Hi-C and RNA-seq.

Curated genetics headlines with links to original reporting. Each item explains the science behind the news at your chosen depth.

SourceCRISPR’s next act: the companies editing the epigenome to treat diseaseJun 26, 2026 · Nature

CRISPREpigeneticsGene therapy

What epigenetic editing does

Epigenetic marks, such as methyl groups on DNA or chemical modifications on histones, control whether a gene is transcribed without altering its sequence. In epigenetic editing, a guide RNA directs a catalytically dead Cas protein (dCas) to a target locus; an attached methyltransferase or activator then writes or erases marks at that site, reducing or boosting gene expression.

Because no DNA strand is cleaved, the approach avoids double-strand break repair pathways and the indels that standard CRISPR–Cas9 editing can introduce at off-target sites.

Companies and conditions in the pipeline

Epicrispr Biotechnologies is developing epigenetic silencing for facioscapulohumeral muscular dystrophy (FSHD), a disorder linked to mis-expression of DUX4; the company presented early trial data in mid-2026. nChroma is pursuing liver-directed silencing of PCSK9 to lower LDL cholesterol, a programme that has shown strong preclinical data in non-human primates but has not yet entered trials. The same company began dosing people with chronic hepatitis B in January 2026.

Delivery varies: some programmes use AAV vectors encoding compact Cas proteins; others use lipid nanoparticles for systemic delivery. All remain investigational; efficacy, durability, and immune responses to repeat dosing are still being evaluated.

Potential advantages and open questions

Advocates argue epigenetic editing reduces risk of off-target mutations and chromosomal rearrangements associated with DNA cleavage. Preclinical data suggest some marks are reversible, unlike permanent sequence changes, though reversal kinetics in human tissues are not fully characterised.

Critics note that epigenetic regulation underpins development and imprinting; broad or persistent silencing outside the target locus could have delayed consequences. Long-term monitoring, dose optimisation, and tissue specificity remain essential before these therapies can be considered established treatments.

Key takeaways

dCas fusion proteins target epigenetic marks at specific loci via guide RNA.
Reported programmes include FSHD, PCSK9 cholesterol silencing, and hepatitis B.
Avoiding DNA cuts may reduce indel risk; long-term safety data are still accumulating.

Curated genetics headlines with links to original reporting. Each item explains the science behind the news at your chosen depth.

lncRNAEpigeneticsRNA–protein interactions

Cis-acting lncRNAs and imprinted silencing

Long non-coding RNAs (lncRNAs) are transcripts longer than ~200 nucleotides with little or no coding potential. Airn and Kcnq1ot1 are imprinted: expressed from the paternal allele, and act in cis, repressing genes across ~15 Mb and ~3 Mb respectively in mouse trophoblast stem cells.

Both recruit Polycomb Repressive Complexes (PRC1 and PRC2), which deposit repressive histone modifications (H2AK119ub by PRC1; H3K27me3 by PRC2), spreading a chromatin state that lowers transcription of target genes.

RIP-seq reveals shared protein partners

The team performed formaldehyde crosslinking RNA immunoprecipitation sequencing (RIP-seq) on 27 proteins in mouse trophoblast stem cells, capturing direct and protein-bridged RNA–protein associations. Protein occupancy profiles along Airn and Kcnq1ot1 correlated more strongly with each other than with Xist or most other chromatin-associated transcripts.

Network analysis showed that the degree to which protein associations partitioned into communities matched how strongly each lncRNA represses its target domain, linking molecular architecture to functional output.

HNRNPU maintains Polycomb marks but not lncRNA tethering

HNRNPU (heterogeneous nuclear ribonucleoprotein U) showed enriched RIP signal over Airn and Kcnq1ot1. CRISPR-mediated depletion of HNRNPU reduced PRC1-directed H2AK119ub and PRC2-directed H3K27me3 across both lncRNA target domains and increased expression of silenced genes in the Airn domain, though genes in the Kcnq1ot1 domain mostly stayed silenced despite the same loss of chromatin marks.

However, HNRNPU loss did not mislocalise Airn or Kcnq1ot1 on chromatin and did not block PRC1 co-occupancy on the transcripts, distinguishing their mechanism from Xist, where HNRNPU has been implicated in chromatin anchoring. HNRNPU depletion also reduced Airn and Xist RNA levels but did not significantly change Kcnq1ot1 abundance.

Key takeaways

Airn and Kcnq1ot1 recruit PRC1/PRC2 to spread H2AK119ub and H3K27me3 over megabase domains.
RIP-seq maps RNA–protein associations; Airn and Kcnq1ot1 profiles are highly correlated.
HNRNPU is required for Polycomb mark maintenance but not lncRNA chromatin tethering.

Genetics news

A genome-wide "switch map" of what each gene does in stem cells

CHARM: reading four layers of a single cell’s genome in one experiment

Epigenome editing: CRISPR tools that change gene activity, not sequence

lncRNAs Airn and Kcnq1ot1: a shared protein partner for long-range gene silencing

A genome-wide "switch map" of what each gene does in stem cells

CHARM: reading four layers of a single cell’s genome in one experiment

Epigenome editing: CRISPR tools that change gene activity, not sequence

lncRNAs Airn and Kcnq1ot1: a shared protein partner for long-range gene silencing