DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
Transcription factors with Perturb-seq knockdown data for MECP2. 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 = MECP2 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 MECP2, 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 |
|---|---|---|---|---|
| chrX:153,875,415–153,875,856 | 222.0 kb | Distal (>10kb) Multiome | 847 | |
| chrX:153,878,887–153,879,684 | 218.5 kb | Distal (>10kb) Multiome | 235 | |
| chrX:153,927,955–153,928,728 | 169.3 kb | Distal (>10kb) Multiome | 711 | |
| chrX:153,934,763–153,935,658 | 162.5 kb | Distal (>10kb) Multiome | 446 | |
| chrX:153,970,913–153,973,065 | 125.2 kb | Distal (>10kb) Multiome | 857 | |
| chrX:154,097,040–154,098,161 | 129 bp | At TSS Multiome | 537 | |
| chrX:154,136,648–154,137,146 | 39.2 kb | Distal (>10kb) Multiome | 391 | |
| chrX:154,368,993–154,370,053 | 271.9 kb | Distal (>10kb) Multiome | 546 | |
| chrX:154,370,757–154,372,188 | 273.7 kb | Distal (>10kb) Multiome | 764 | |
| chrX:154,378,063–154,379,701 | 281.3 kb | Distal (>10kb) Multiome | 687 |
Genomic view of the MECP2 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.