Lab Activities

Laboratory for Regulatory Genomics

Research Activities

Chung-Chau Hon portrait

Team Director

Chung-Chau Hon

Our team investigates how gene regulatory mechanisms contribute to human disease, with a particular focus on cis-regulatory elements (CREs), which play central roles in controlling gene expression. By combining large-scale single-cell profiling of CRE activity with advanced computational and deep learning approaches, we seek to understand how genetic variation influences gene regulation in a cell-type-specific manner. To support this effort, we developed computational methods for identifying transcribed cis-regulatory elements (tCREs) at single-cell resolution and generated a comprehensive atlas of tCRE activity across human tissues. Building upon this resource, we established an analytical framework that integrates single-cell tCRE data with genome-wide association studies (GWAS) to quantify trait heritability at single-cell resolution. This approach uncovered fine-scale associations between diverse cellular populations and more than 12,000 human traits and diseases and has been made available through an interactive online database (Figure). We are currently applying these methodologies to large disease cohorts, including single-cell datasets from patients with amyotrophic lateral sclerosis (ALS), ulcerative colitis (UC), and acute myeloid leukemia (AML), to identify disease-relevant cell states and regulatory programs. In parallel, we are developing deep learning models that predict gene expression directly from DNA sequence by integrating large-scale tCRE and epigenomic datasets. The training dataset encompasses regulatory genomic data from 83 eukaryotic species, including plants, fungi, insects, fish, and mammals, enabling the model to learn conserved regulatory DNA grammar across evolutionary lineages. These models support in silico mutagenesis, allowing systematic prediction of how genetic variants alter regulatory activity and gene expression. In benchmarking analyses of expression quantitative trait locus (eQTL) prediction, the model achieved superior performance compared with existing state-of-the-art approaches. Together with our cell type-specific framework for linking distal CREs to their target genes, these approaches provide a comprehensive platform for interpreting the regulatory consequences of genetic variation. Ultimately, this work advances our understanding of gene regulation in health and disease and facilitates the functional interpretation of disease-associated genetic variants.

Single-Cell Regulatory Elements and Traits Encyclopedia (SCREATE).

Laboratory for Regulatory Genomics figure

Single-Cell Regulatory Elements and Traits Encyclopedia (SCREATE).

Laboratory for Regulatory Genomics figure

A) Overview of SCREATE, an online resource comprising more than one million cells from 32 human tissues, over 526,000 transcribed cis-regulatory elements (tCREs), and single-cell-resolution heritability enrichment profiles for more than 120,000 GWAS traits. B) User interface of SCREATE displaying the heritability enrichment landscape of gallstone disease across all cell populations. Gallstone disease heritability is strongly enriched in hepatocytes, highlighting their central role in disease pathogenesis. C) Zoomed-in view of the hepatocyte compartment for gallstone disease heritability enrichment. Users can interactively explore cell clusters and access detailed annotations of individual cell subpopulations (top right).

A) Overview of SCREATE, an online resource comprising more than one million cells from 32 human tissues, over 526,000 transcribed cis-regulatory elements (tCREs), and single-cell-resolution heritability enrichment profiles for more than 120,000 GWAS traits. B) User interface of SCREATE displaying the heritability enrichment landscape of gallstone disease across all cell populations. Gallstone disease heritability is strongly enriched in hepatocytes, highlighting their central role in disease pathogenesis. C) Zoomed-in view of the hepatocyte compartment for gallstone disease heritability enrichment. Users can interactively explore cell clusters and access detailed annotations of individual cell subpopulations (top right).

Recent Major Publications

  1. Ikedo A, Aoki R, Sakai H, Saeki N, Yanagihara Y, Moody J, Kojima M, Kouno T, Ando Y, Hino K, Kinoshita T, Carninci P, Shin JW, Hon C, Uezumi A, Kamei Y, Imai Y. Estrogen signaling in PDGFRα+ cells positively regulates cortical bone metabolism via IGFBP5 in female mice. JBMR Plus 10, ziaf178 (2025)

  2. Inamo J, Takeshita M, Suzuki K, Tsunoda K, Usuda S, Kuramoto J, Moody J, Hon C, Ando Y, Sasaki T, Yoshitake K, Mitsuyama S, Asakawa S, Kanai Y, Takeuchi T, Kaneko Y. Comparative single-cell and spatial profiling of anti-SSA-positive and anti-centromere-positive Sjögren’s disease reveals common and distinct immune activation and fibroblast-mediated inflammation. Nat Commun 16, 8299 (2025)

  3. Kudo Y, Miyamoto K, Suzuki S, Chida A, Tojo A, Hasegawa M, Shigehara A, Koya I, Ando Y, Sato M, Kondo A, Kumagai T, Deguchi H, Sugiyama Y, Ito Y, Shirosaki K, Yamagishi S, Maeda Y, Kanamori H, Kano M, Kato M, Tsujikawa H, Yoshimatsu Y, Takabayashi K, Okabayashi K, Kanai T, Hosoe N, Kato M, Moody J, Hon C, Kuroda T, Yamada Y, Fujino A, Sujino T. Longitudinal single-cell analysis of glucagon-like peptide-2 treatment in the patients with short bowel syndrome. JCI Insight 10, e194497 (2025)

  4. Luginbuehl J, Prabhu AV, Yip CW, Ando Y, Leon J, Yasuzawa K, Hon CC, Moody J, Roudnicky F, Kremer T, Shin JW. Defining the Cis-Regulatory Elements of SCN1A in GABAergic Interneurons. Mol Neurobiol 62, 15730-15740 (2025)

  5. Handa M, Takiuchi T, Kawaguchi S, Hon C, Moody J, Okazaki Y, Ozaki K, Horie M, Ohara Y, Doshida M, Takeuchi T, Matsubayashi H, Saji F, Miyake T, Ishikawa T, Ando Y, Komukai S, Kitamura T, Shin JW, Kimura T. Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single cell analysis. Reprod Biomed Online 51, 104833 (2025)

  6. Saito Y, Ishikawa M, Ohkuma M, Moody J, Mabuchi Y, Sanosaka T, Ando Y, Yamashita T, Hon C, Shin JW, Akamatsu W, Okano H. NEUROD1 efficiently converts peripheral blood cells into neurons with partial reprogramming by pluripotency factors. Proc Natl Acad Sci U S A 122, e2401387122 (2025)

  7. Kock K, Tan L, Han K, Ando Y, Jevapatarakul D, Chatterjee A, Lin Q, Buyamin E, Sonthalia R, Rajagopalan D, Tomofuji Y, Sankaran S, Park M, Abe M, Chantaraamporn J, Furukawa S, Ghosh S, Inoue G, Kojima M, Kouno T, Lim J, Myouzen K, Nguantad S, Oh J, Rayan N, Sarkar S, Suzuki A, Thungsatianpun N, Venkatesh P, Moody J, Nakano M, Chen Z, Tian C, Zhang Y, Tong Y, Tan C, Tizazu A, Loh M, Hwang Y, Ho RC, Larbi A, Ng T, Won H, Wright FA, Villani A, Park J, Choi M, Liu B, Maitra A, Pithukpakorn M, Suktitipat B, Ishigaki K, Okada Y, Yamamoto K, Carninci P, Chambers JC, Hon C, Matangkasombut P, Charoensawan V, Majumder PP, Shin JW, Park W, Prabhakar S. Asian diversity in human immune cells. Cell 188, 2288-2306.e24 (2025)

Invited Presentations

  • Hon C, Yang M. "Beyond Karyotype: Heterogeneity of Gene Regulatory Programs in Acute Myeloid Leukemia." The 84th Annual Meeting of the Japanese Cancer Association, Kanazawa, Japan, September 25–27 (2025)

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