Christopher H. Douse

De novo missense variants in TRIM28 identified in individuals with neurodevelopmental delay show features of transposable element activation

TRIM28 missense variants in individuals with neurodevelopmental delay disrupt epigenetic control of transposable elements, leading to altered gene expression and neurodevelopmental defects.

A framework for efficient CRISPRi-mediated silencing of retrotransposons in human pluripotent stem cells

This paper describes a protocol for CRISPRi-mediated silencing of retrotransposons in hiPSCs, validated using a multiome approach combining RNA-seq, CUT&RUN, and proteomics.

Loss of SETDB1-mediated H3K9me3 in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons

This study shows that loss of H3K9me3 in human neural progenitor cells activates L1 retrotransposons by reducing CpG methylation at their promoters.

Retroviral insertions contributed to the divergence of human and chimpanzee brains

This study identifies a chimpanzee-specific retroviral insertion that influences gene regulation and brain development, highlighting its role in human-chimpanzee brain divergence.

LINE-1 retrotransposons regulate the exit of human pluripotency and early brain development

This study shows that L1 retrotransposons influence human pluripotency exit and early brain development through their expression and derived transcripts.

MORC2 directs transcription-dependent CpG methylation of human LINE-1 transposons in early neurodevelopment

This study shows MORC2 regulates CpG methylation of active LINE-1 retrotransposons during human neurodevelopment, similar to the piRNA pathway in the germline.

DNA methylation governs the sensitivity of repeats to restriction by the HUSH-MORC2 corepressor

The paper shows that DNA methylation and the HUSH-MORC2 complex independently regulate repeat elements in human neural progenitor cells, with MORC2 binding increasing in demethylated regions.

The annotation and function of the Parkinson's and Gaucher disease-linked gene GBA1 has been concealed by its protein-coding pseudogene GBAP1

The paper shows that sequencing ambiguity between GBA1 and its pseudogene GBAP1 affects transcriptomic analysis, revealing non-lysosomal functions in the brain and widespread annotation inaccuracies.

L1 retrotransposons drive human neuronal transcriptome complexity and functional diversification

This study shows L1 retrotransposons contribute to human brain transcriptome complexity and functional diversification through cell-type specific transcripts and regulatory RNAs.

Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease

The paper shows that ZNF91 creates mini-heterochromatin domains that limit the regulatory impact of SVA transposons in human neural progenitor cells, contributing to XDP pathology.

TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control

The paper identifies TASOR as a pseudo-PARP essential for HUSH complex assembly and epigenetic repression of transposons.

A human-specific structural variation at the ZNF558 locus controls a gene regulatory network during forebrain development

The paper identifies a human-specific structural variation at the ZNF558 locus that regulates a gene network involved in forebrain development by controlling SPATA18 expression through a VNTR contraction.