L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]
Transcription factors with Perturb-seq knockdown data for GRM4. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = GRM4 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of GRM4, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr6:33,771,283–33,772,101 | 284.6 kb | Distal (>10kb) Multiome | 478 | |
| chr6:33,788,007–33,789,360 | 267.2 kb | Distal (>10kb) Multiome | 999 | |
| chr6:34,052,159–34,053,582 | 2.7 kb | Proximal (<10kb) | 133 | |
| chr6:34,053,863–34,054,069 | 2.3 kb | Proximal (<10kb) | 57 | |
| chr6:34,055,337–34,055,520 | 802 bp | At TSS | 189 | |
| chr6:34,056,249–34,056,753 | 145 bp | At TSS Multiome | 192 | |
| chr6:34,143,812–34,144,483 | 87.8 kb | Distal (>10kb) Multiome HiCAR | 304 | |
| chr6:34,144,948–34,146,170 | 89.4 kb | Distal (>10kb) Multiome HiCAR | 310 | |
| chr6:34,196,308–34,196,855 | 140.2 kb | Distal (>10kb) Multiome | 723 | |
| chr6:34,202,245–34,203,164 | 146.5 kb | Distal (>10kb) Multiome | 90 | |
| chr6:34,223,440–34,224,542 | 167.7 kb | Distal (>10kb) Multiome | 795 | |
| chr6:34,234,536–34,237,980 | 179.1 kb | Distal (>10kb) Multiome | 1100 | |
| chr6:34,246,464–34,249,721 | 190.4 kb | Distal (>10kb) Multiome | 1030 |
Genomic view of the GRM4 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.