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LOC106096416 KRT18 locus control region [ Homo sapiens (human) ]

Gene ID: 106096416, updated on 10-Oct-2023

Summary

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Gene symbol
LOC106096416
Gene description
KRT18 locus control region
Gene type
biological region
Feature type(s)
misc_feature: conserved_region
mobile_element
protein_bind
regulatory: DNase_I_hypersensitive_site, enhancer, enhancer_blocking_element, locus_control_region, promoter, silencer, transcriptional_cis_regulatory_region
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
This region contains multiple positive and negative regulatory elements spanning the KRT18 (keratin 18) gene region, which function together to control the tissue-specific, copy number dependent, and integration-site independent expression of KRT18. These elements include a 5' opposite orientation Alu element, whose transcription is required to modulate copy number dependent expression of the adjacent gene. The Alu element can also function independently as an enhancer, insulator, and enhancer blocker, depending on the context. Additional positive regulatory elements in this region include a cryptic promoter upstream of the canonical KRT18 promoter, an enhancer within the first intron, and a regulatory element in the sixth exon. Activity of the element in the sixth exon can be disrupted by a frameshifting mutation that decreases the stability of the KRT18 transcript. A subregion overlapping the 5' portion of the gene was validated as an active enhancer by the STARR-seq (self-transcribing active regulatory region sequencing) massively parallel reporter assay (MPRA) in HCT116 colorectal carcinoma cells, where it was defined as a group 2 enhancer that depends on the BRD2, BRD4, P300/CBP, MED14 and CDK7 cofactors, with strong dependence on CDK7. Two subregions were also shown to be active enhancers by ChIP-STARR-seq in primed human embryonic stem cells, where both are associated with the NANOG transcription factor and are marked by the H3K27ac and H3K4me1 histone modifications. Another subregion located upstream of the gene was also validated as a functional repressive element by Sharpr-MPRA (Systematic high-resolution activation and repression profiling with reporter tiling using massively parallel reporter assays) in HepG2 liver carcinoma cells (group: HepG2 Repressive non-DNase unmatched - State 2:TssF, active promoter, flanking TSS/CpG islands). This locus also includes three accessible chromatin subregions that were validated as silencers based on their ability to repress an origin of replication minimal core promoter by the ATAC-STARR-seq (assay for transposase-accessible chromatin with self-transcribing active regulatory region sequencing) MPRA in GM12878 lymphoblastoid cells. [provided by RefSeq, May 2023]
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Genomic context

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Location:
12q13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (52947765..52956706)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (52912321..52921248)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (53341823..53350490)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr12:53287796-53287974 Neighboring gene Sharpr-MPRA regulatory region 10212 Neighboring gene ribosomal protein L7 pseudogene 41 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:53292699-53293198 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:53295217-53296061 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4486 Neighboring gene microRNA 9898 Neighboring gene keratin 8 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:53311823-53312324 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:53312325-53312824 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53337539-53338133 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:53339323-53339918 Neighboring gene Sharpr-MPRA regulatory region 15494 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53358683-53359326 Neighboring gene keratin 18 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53365007-53365934 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53365935-53366860 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:53397033-53397195 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53399611-53400354 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53400355-53401098 Neighboring gene eukaryotic translation initiation factor 4B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6400 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6401 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4490 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53441165-53442009 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53442010-53442853 Neighboring gene TNS2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6402 Neighboring gene tensin 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Bibliography

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Related articles in PubMed

  1. A regulatory element of the human keratin 18 gene with AP-1-dependent promoter activity. Rhodes K, et al. J Biol Chem, 1998 Oct 9. PMID 9756890
  2. Development of an epithelium-specific expression cassette with human DNA regulatory elements for transgene expression in lung airways. Chow YH, et al. Proc Natl Acad Sci U S A, 1997 Dec 23. PMID 9405675, Free PMC Article
  3. Methylation of an ETS site in the intron enhancer of the keratin 18 gene participates in tissue-specific repression. Umezawa A, et al. Mol Cell Biol, 1997 Sep. PMID 9271368, Free PMC Article
  4. Contrasting effects of the SATB1 core nuclear matrix attachment region and flanking sequences of the keratin 18 gene in transgenic mice. Neznanov N, et al. Mol Biol Cell, 1996 Apr. PMID 8730098, Free PMC Article
  5. Alu sequence involvement in transcriptional insulation of the keratin 18 gene in transgenic mice. Thorey IS, et al. Mol Cell Biol, 1993 Nov. PMID 7692231, Free PMC Article

See all (22) citations in PubMed

GeneRIFs: Gene References Into Functions

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See Variation Viewer (GRCh37.p13)

General gene information

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Other Names

  • ATAC-STARR-seq lymphoblastoid silent region 4487
  • ATAC-STARR-seq lymphoblastoid silent region 4488
  • ATAC-STARR-seq lymphoblastoid silent region 4489
  • CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:53343308-53344507
  • NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53342297-53342890
  • NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:53342891-53343484
  • Sharpr-MPRA regulatory region 294

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_042295.2 

    Range
    101..9042
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    52947765..52956706
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    52912321..52921248
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version

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