Biology subjects

Chuang, R.

Publications and source records attributed to Chuang, R..

4 recordsLinked to original sources

bioRxiv2026

J-domain proteins bridge the PKL and ATRX complex to transcription factors to fine-tune gene expression via H3.3 deposition

Epigenetic modifications, including histone modifications and DNA methylation, direct gene expression programs during the growth and development of eukaryotic organisms. In Arabidopsis thaliana, the chromatin remodeler PICKLE (PKL), a homolog of animal CHD3, plays a critical role during these processes. Previous studies of PKL have painted a complex picture of its function, including both activating and repressive roles, however, how PKL can control both transcriptional silencing and activation is unknown. We have identified a group of J-domain-containing proteins (DNAJs), usually known for their roles in protein folding, that guide PKL recruitment to various gene promoters by bridging PKL to transcription factors. Mutation of PKL's DNAJ-interacting domain disrupts PKL association with chromatin. Once recruited to transcription factor-bound sites, PKL coordinates with the histone chaperone ATRX to deposit HISTONE3.3 (H3.3) at targeted loci, which also negatively affects the accumulation of H3 lysine 27 trimethylation (H3K27me3) at promoters. We found that transcriptional outcome of PKL binding depends not only on the changes in H3.3 occupancy but also on the pre-existing chromatin context at PKL-targeted sites. Our findings outline a new mechanism for CHD3 chromatin remodeler recruitment and function.

plant biology↗

bioRxiv2026

Multiple redundant mechanisms account for the majority of gene silencing downstream of DNA methylation

DNA methylation is a conserved epigenetic modification crucial for silencing genes and transposable elements (TEs). However, the mechanisms that cause silencing remain unclear, partly because methyl reader protein mutants in both plants and animals show minimal transcriptional changes. To explore the possibility of redundancy among these silencing mechanisms, we generated combinatorial mutants of H1.1, H1.2, ADCP1, MOM1, MBD2, MBD5, and MBD6 lacking key methyl readers and related silencing pathways. We observed massive derepression of genes and TEs at DNA-methylated loci, showing that these pathways account for 73% of silencing compared to DNA methylation-free mutants. We also observed that immune response genes were upregulated, causing an imbalance between growth and defense. Loss of downstream silencing pathways further disrupted 3D genome organization, leading to increased euchromatin-heterochromatin interactions. These findings highlight the cooperative action of multiple downstream mechanisms in DNA methylation-mediated silencing and genome organization.

molecular biology↗

bioRxiv2025

CDCA7 facilitates MET1-mediated CG DNA methylation maintenance in centromeric heterochromatin via histone H1

DNA methylation is a conserved epigenetic modification essential for maintaining genome stability. However, how methyltransferases maintain CG methylation within compact chromatin, including centromeres, remains unclear. In humans, CDCA7 is necessary for the inheritance of DNA methylation at juxta-centromeres. Mutations that impair its ability to bind chromatin result in Immunodeficiency, Centromeric Instability, and Facial Anomalies (ICF) syndrome, characterized by centromeric instability. To investigate whether CDCA7 function is conserved, we identified two Arabidopsis thaliana orthologs, CDCA7A and CDCA7B. The loss of both copies results in CG hypomethylation at pericentromeric regions and centromeric satellite repeat arrays. Machine learning analysis suggested that heterochromatic nucleosomes, with enrichment of H1, H2A.W, and H3K9me2 levels, depend heavily on CDCA7 proteins for CG methylation maintenance of the associated DNA. Loss of H1 restores heterochromatic DNA methylation in cdca7a cdca7b mutants, indicating that CDCA7A and CDCA7B mainly remodel H1-containing nucleosomes for methyltransferases to access DNA. Notably, in h1.1 h1.2 mutants, CG methylation shows a significant increase in centromeres, which reveals a new inhibitory role of H1 in DNA methylation maintenance within satellite repeat arrays. Centromeric DNA hypermethylation is lost in h1.1 h1.2 cdca7a cdca7b quadruple mutants, demonstrating that CDCA7A and CDCA7B can act independently of H1 to enhance MET1 activity. Overall, these findings establish CDCA7A and CDCA7B as conserved regulators of DNA methylation within heterochromatin and centromeric satellite repeat arrays.

molecular biology↗

bioRxiv2020

The Genomic Formation of Human Populations in East Asia

The deep population history of East Asia remains poorly understood due to a lack of ancient DNA data and sparse sampling of present-day people. We report genome-wide data from 191 individuals from Mongolia, northern China, Taiwan, the Amur River Basin and Japan dating to 6000 BCE - 1000 CE, many from contexts never previously analyzed with ancient DNA. We also report 383 present-day individuals from 46 groups mostly from the Tibetan Plateau and southern China. We document how 6000-3600 BCE people of Mongolia and the Amur River Basin were from populations that expanded over Northeast Asia, likely dispersing the ancestors of Mongolic and Tungusic languages. In a time transect of 89 Mongolians, we reveal how Yamnaya steppe pastoralist spread from the west by 3300-2900 BCE in association with the Afanasievo culture, although we also document a boy buried in an Afanasievo barrow with ancestry entirely from local Mongolian hunter-gatherers, representing a unique case of someone of entirely non-Yamnaya ancestry interred in this way. The second spread of Yamnaya-derived ancestry came via groups that harbored about a third of their ancestry from European farmers, which nearly completely displaced unmixed Yamnaya-related lineages in Mongolia in the second millennium BCE, but did not replace Afanasievo lineages in western China where Afanasievo ancestry persisted, plausibly acting as the source of the early-splitting Tocharian branch of Indo-European languages. Analyzing 20 Yellow River Basin farmers dating to [~]3000 BCE, we document a population that was a plausible vector for the spread of Sino-Tibetan languages both to the Tibetan Plateau and to the central plain where they mixed with southern agriculturalists to form the ancestors of Han Chinese. We show that the individuals in a time transect of 52 ancient Taiwan individuals spanning at least 1400 BCE to 600 CE were consistent with being nearly direct descendants of Yangtze Valley first farmers who likely spread Austronesian, Tai-Kadai and Austroasiatic languages across Southeast and South Asia and mixing with the people they encountered, contributing to a four-fold reduction of genetic differentiation during the emergence of complex societies. We finally report data from Jomon hunter-gatherers from Japan who harbored one of the earliest splitting branches of East Eurasian variation, and show an affinity among Jomon, Amur River Basin, ancient Taiwan, and Austronesian-speakers, as expected for ancestry if they all had contributions from a Late Pleistocene coastal route migration to East Asia.

genomics↗