Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis
Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as in vivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.
Authors
- Axel Visel (ORCID: https://orcid.org/0000-0002-4130-7784)
- Ming Hu (ORCID: https://orcid.org/0000-0003-0987-2916)
- Alex S. Nord (ORCID: https://orcid.org/0000-0003-4259-7514)
- Susan Lindtner
- John L.R. Rubenstein (ORCID: https://orcid.org/0000-0002-4414-7667)
- Diane E. Dickel (ORCID: https://orcid.org/0000-0001-5497-6824)
- L Pennacchio (ORCID: https://orcid.org/0000-0002-8748-3732)
- Karol Cichewicz (ORCID: https://orcid.org/0000-0001-5926-3663)
- Armen Abnousi (ORCID: https://orcid.org/0000-0003-1822-0928)
- Ian Jones (ORCID: https://orcid.org/0000-0001-5821-5889)
- Rinaldo Catta-Preta (ORCID: https://orcid.org/0000-0001-9833-1278)
- James D. Price (ORCID: https://orcid.org/0000-0001-6127-1451)
- Ivan Jurić (ORCID: https://orcid.org/0000-0002-1076-6320)
- Jennifer A. Akiyama (ORCID: https://orcid.org/0000-0002-0667-9355)
- Nicolas Seban (ORCID: https://orcid.org/0000-0002-6737-6681)
- Athéna R. Ypsilanti (ORCID: https://orcid.org/0000-0002-0310-7693)
- Linda Su-Feher (ORCID: https://orcid.org/0000-0002-0660-7925)
- Sally A. Boerma (ORCID: https://orcid.org/0000-0002-2764-1452)
- Yurong Wang (ORCID: https://orcid.org/0000-0003-3988-2808)
- Yin Shen
Institutions
- Cleveland Clinic (US)
- Lawrence Berkeley National Laboratory (US)
- University of California, San Francisco (US)
- Joint Genome Institute (US)
- University of California, Davis (US)
Publication Details
- Journal
- Developmental Cell
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1016/j.devcel.2024.10.004
- Citations
- 14
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 3.04