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| Status |
Public on Apr 12, 2023 |
| Title |
MAPT expression is mediated by long-range interactions with cis-regulatory elements [scMultiomics] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Tau is encoded by MAPT and abnormal aggregates of tau are a hallmark of a group of neurodegenerative diseases called tauopathies. MAPT is lowly expressed in neural progenitor cells (NPCs), but it is more highly expressed in oligodendrocytes, astrocytes, and neurons that derive from NPCs. This expression switch at differentiation suggests that MAPT expression is controlled by transcription factors and cis-regulatory elements specific to these differentiated cell types, including neurons.
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| Overall design |
We performed HiC and three-dimensional chromatin conformation capture (Capture-C), single-nucleus multiomics (RNA-seq and ATAC-seq), bulk ATAC-seq, and ChIP-seq for H3K27Ac and CTCF in neurons differentiated from human iPSC cultures. From these methods, we nominated candidate cis-regulatory elements (cCREs) for MAPT in human NPCs, NPCs differentiated to neurons, and pure inhibitory or excitatory neuron cultures. We then functionally assessed nominated regions using luciferase assays and CRISPR dCas9-KRAB inhibition experiments to assess the effect of nominated regions on MAPT expression.
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| Contributor(s) |
Rogers BB, Anderson AG, Cochran JN |
| Citation(s) |
37090552 |
| |
| Submission date |
Mar 23, 2023 |
| Last update date |
Nov 21, 2023 |
| Contact name |
J. Nicholas Cochran |
| E-mail(s) |
ncochran@hudsonalpha.org
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| Phone |
2563275220
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| Organization name |
HudsonAlpha Institute for Biotechnology
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| Lab |
Cochran Lab
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| Street address |
601 Genome Way
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| City |
Huntsville |
| State/province |
AL |
| ZIP/Postal code |
35806 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE228121 |
MAPT expression is mediatedd by long-range interactions with cis-regulatory elements. |
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| Relations |
| BioProject |
PRJNA948138 |
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