NONHSAT119717

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HOTTIP, A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression.

Annotated Information

Approved Symbol: HOTTIP

Approved Name: HOXA transcript at the distal tip

LncBook ID: HSALNT0120390

Characteristics

HOTTIP gene located at 5°Ø end of HoxA cluster, bidirectional transcript with HOXA13 ref1. It is ~3.8kb, transcript in human, spliced and polyadenylated [1] HOTTIP have ~2.3kb transcript in mouse, different splice isoforms, currently known transcripts initiate downstream from the syntenic site in human. HOTTIP contains some highly conserved sequences which are predicted to form a conserved structure [2]

Function

HOTTIP Controls activation of HOXA genes. Chromosomal lopping bring it into close association with gene loci. HOTTIP binds WDR5 and recruits a MLL chromatin modifiying complex to maintain a domain of active chromatin over the of HOXA cluster [1]. HOTTIP controls activation of HOXA genes in mammals and chicken. The impact on HOXA genes decreases with increased genomic distance from HOTTIP. Phenotypic impact in chicken forelimb of HOTTIP knockdown was shorter than normal distal bones. HOTTIP doesnot affect chromosomal structure and looping but it is necessary for maintenance of H3 K4me3 chromatin marks over the distally expressed half of the HOXA locus. HOTTIP RNA binds WDR5 a component of MLL/Trithorax complexes recruiting a MLL complex to lay down H3 K4me3 marks. WDR5 binding mediated by sequence(s) in 1kb of HOTTIP. It appears to act in cis, its function is facilitated by the chromosomal looping that brings it into close proximity with HOXA genes. Portions of HOXA13as sequence are well conserved throughout mammals. HOTTIP Appears to be present in chicken although there is little homology [2] HOTTIP contains some highly conserved sequences which are predicted to form a conserved structure [2].

Regulation

There is mutual interdependence between HOTTIP and WDR5 in terms of regulation [1].

Disease

  • Hirschsprung [3]
  • Malignant Glioma [4]
  • Pancreatic cancer [5]

Expression

HOTTIP shows collinear regulation of expression like HOX protein coding genes ref1. HOTTIP has bivalent chromatin marks (both H3 K4me3 and H3 K27me3) whether expression off or on, but only expressed in more distal cells [1]. HOTTIP has a similar expression profile to HOXA13, expressed in colon, prostate, placenta and uterus, as well as hand, foreskin and foot fibroblasts [2][1].

Labs working on this lncRNA

  • Department of Gynaecology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China
  • Howard Hughes Medical Institute, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Department of Dermatology, University of California San Francisco (UCSF), San Francisco, CA 94115, USA.
  • Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Program in Gene Function and Expression, Dept. of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical school, Worcester, MA, USA.
  • Howard Hughes Medical Insti

References

  1. 1.0 1.1 1.2 1.3 1.4 Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression[J]. Nature. 2011, 472(7341):120-U158.
  2. 2.0 2.1 2.2 2.3 Sasaki YTF, Sano M, Kin T, Asai K & Hirose T. Coordinated expression of ncRNAs and HOX mRNAs in the human HOXA locus[J]. Biochem Bioph Res Co. 2007, 357(3):724-730.
  3. Xie H, Zhu DM, Xu C, Zhu HR, Chen PF, Li HX et al. Long none coding RNA HOTTIP/HOXA13 act as synergistic role by decreasing cell migration and proliferation in Hirschsprung disease[J]. Biochem Bioph Res Co. 2015, 463(4):569-574.
  4. Xu LM, Chen L, Li F, Zhang R, Li ZY, Chen FF et al. Over-expression of the long non-coding RNA HOTTIP inhibits glioma cell growth by BRE[J]. J Exp Clin Canc Res. 2016
  5. Fu ZQ, Chen CH, Zhou QB, Wang YX, Zhao Y, Zhao XH et al. LncRNA HOTTIP modulates cancer stem cell properties in human pancreatic cancer by regulating HOXA9[J]. Cancer Lett. 2017

Sequence

>gi|100316868|ref|>NR_037843.3|Homo sapiens HOXA distal transcript antisense RNA (HOTTIP), long non-coding RNA

000001 CCCTTCCTTT ATCCCAGTGG GGCCCAGACC CGCGCAACCA GGCGGGGAGG GGAGGTGGGC GCGCGATTGG GTTGCGATCT 000080
000081 GGAGCAGTGG GGACAGGTCA GGAACCGGCG CGTATTTCTG CAGTGAGACC ACAGGACGGA CATCGGCGCC TTCGGCTTCG 000160
000161 ATGGAGTTGC GATTTTGCTC TTTCCAGGGA AACAGTGGCA GGGTGTTTGC TGCTTATCGG TTCCTGCGGA TATGCCTGGG 000240
000241 TCCCAGGACA TTCCACTGGA GGCTTGGACT GCATTTAGGA GCCCCTATCC CTTCCCTGTC CACACTGTTA GTGAGCAATT 000320
000321 TCATATGTTT GCATTTAGAC CCATAGACTC AGAACGACTC ATCACACACA CACACAGTGT ACACTGACAC ACTCACATTC 000400
000401 GCACACTTAG GTATACAGCC TGATCCTTGC TCTGACCTGG TAACAACGCT TCCTCCTCCA GAGACTTTGA GATAGAGCGA 000480
000481 GCGATCCCTG TGCACCATTC ATCCATGCTC CCACCTCGCC AGTATGGCTG GCTTAGTTCT GGAAGGGGCT TAAGAGGAAC 000560
000561 AAGCCCCAGC TGTGCTTCTG GCTGGGACTT AAACCCCCCT TCTGGGCCCT AAAGCCACGC TTCTTTGTGG ACCGGACCTG 000640
000641 ACTCTCCAGG AATCTGGGAA CCCGCTATTT CACTCTATTT TGGGACAAGA AAAAGGGGCT CTTTGGGGCC ACTTCCTGCC 000720
000721 TTCCCCTCAA GTAGGATCTC CAGCCTGCAG AGGGTGCCTA GTCCTTCTTT GCCCAAGAAC CAGTCCAAGA AGCCTTTCCT 000800
000801 CTGTGCCTGG GAAATGCAAC CTTTTCTTGG GAGCATGGTA GGGTGTTGGT GCTGAAGAAC CAAGCAGCGA CCCGTCTTGT 000880
000881 AGCTGCCATG TTTTGTCGAG GGGTTCTGGG GGTCCTGCTG CTTTAGAGCC ACATACTTCC ACTTCCTGAT TCACTACTGT 000960
000961 GAGCTGGTCA GATGCCTAGA AGAGGAACAA GCGTTCAAAG TGAAAGTGGG CACATTACCG GAATAGTGCT GGGGAGAGTG 001040
001041 CTGGATTCTT TTCCACCCCA GGCGGACTGG TGAGAAGCCA GGCTTGGACC TGTCCTCTGC TCCTAGCTTG CACACTCAGC 001120
001121 CCTAAACTCA GAGCAGCACG CATACCACCC CTCACACACA CCCCACCATC TGCTGTCTAA GGCCCCTGGG CTTCCTGCAG 001200
001201 GATCCAGACC AATGTGGCTG GGCTTGGGCT TTTATCTGTC CTGATCCTGG ATTTGTCCTG ACCAATGTAA GTGTCGCCCA 001280
001281 ATAAAACCTT CTATGACCCC CACACCAGCC ACCCCCCCAC CAAGTGTGCC CTTTCCTTCT TGACTTTTTA GCAGTTCTGG 001360
001361 GTAAATATTG ATTTGCCCCC AGTTTACCTT CTCCCTGACT GGCCATTTGC AGACTCAGGA ACTAGCCTCT GTAGGGACTT 001440
001441 GATTTTTCTG TTACTTTCTG GCCGTTTCAC CACCCCCCTT CCTCCCTCCA AGTGGCATTG TAAAACTCAC AGTGACAAAG 001520
001521 AGACAGAGTA GGGTTCTAGG CCCCTGTTCC TGGGGACTTG AAGGCGGTTT TACATACTGG TCAGACACGG CTGGAGGCCA 001600
001601 AGGTCAAGTT GAAAGTTGCA GTCCAGCCAG CATGAGAACT GCCATGCGAG CGTAGAGACA CAGGCAGCAG CAAAAGGCCC 001680
001681 ATTGCCCACA TCCCCTCACT CTTAATTTTC TCTCTCTTTT TAAAATTCTC GCCTCTGACT CTGTTCGGCT GCCCAGAATT 001760
001761 TTTTGGTGCC TTCGTGGGGT TTTTGGGGCG GTGTTTACCG ACTCTTCTCT GCCTCCGCCC TGCTCAGCCA GGGCTTTGAG 001840
001841 CCTCTTCGGT TTTCCGGCCA GACCCGGAAA AACGAAAACA CAGCTTGGGG AGCCCCCACT AGCCGGCGCC TGTGCCAGCT 001920
001921 CACCTCTGGC CATGGCGCAG CTGCCGGTGC ACACGGCGGC CAAGGCCAGC TCCACATTCT TCCCTCCCCC TCCCACTTCA 002000
002001 CCGTAGCCCC GAACCCTGCG CGCAGAGAAA GGGTCTCAGC TCCACAGACG ACTGGGTCCC TCCTCACCAA AAATGGTGAG 002080
002081 ACAAGATTTC ATCTGTCGGC CGAGGAGCCA CAAGCAGGTA CCACAAAGCC ACTAGTGCAC AGGGACTCAG AAAAGACGGC 002160
002161 AGGAGCCCAA GGAAAACTCC AATTTGAGTA CAGCCCTGCC TTGTTTCCCC CAGAGAGTCC CTGAGCAAGG AGACCTCCAC 002240
002241 CCCACACACA CCATTTCAGA ACAACCAGGT TCCAGACTCC CATGAGGAGC ATCTCCCACT GCAGAGCCTT GGCCAGCCGC 002320
002321 GCCCGGACTC CTCAGAGCTG GCGCAAACTC CGTCCTCCAA AACTCGGCTC TGGGAGGCCT AAGTGACTCC GAAGCCGGCG 002400
002401 GCAGCCGCGG CAGCGGCCGT GGTGGTGGAA GAGCTCTTTT CCCCGACAGT GCCACTGATC GCTCTTCACT GGAGCTGGAA 002480
002481 ACAGCCTTCG CGGAAAGGAC CGGAGCATGC GTTAGAAGCA GAGGGAGCTT GGTGAAGGGC TCGGCTGGAA GGAGGAAACG 002560
002561 CCTTCTCGCA GTGCGCGGCC AGCCCGCGGG GGACACCGGC TTGCTGGACT GCAGGGGCCC GTGCCACCCA GGAAGTGACC 002640
002641 TGCGGGTCAC TCAGCCGGGG CGCTGGGCGA GCGCGGGACG GCCCGGAGAA TTCCGTGCGG CTGCGACGGG AAAAGGACGA 002720
002721 GGGGTCTCTG TACCCGACGC TGCCACTGGC CCAAAGGAAT TTTACCCGCG AGCGCCCACC CCACCCTAGC TTGATGCTTA 002800
002801 CGCCCGCAAC AAAACAGGAA ACCAGGACTG GGCAGTGCAT TCTTTAAGTC AACAAATACA CTGAAGACTT CGAGCGTTTG 002880
002881 AAGGAAGGAG GGGGTTTGCA CGTAAGCCTG GCCCCGCCGG GCTCGGCTTT CTCGCTGAGA AAGCGGCGCA GGCAGCCAGG 002960
002961 CGGCCTGGGC CCGCGGGGGT CCATCTCGCC CTAGACTCCT AAGAACTCCC ACGGCCCTGT TCCCAGCTGC GAATTCTTAA 003040
003041 TGCACAACGC GACGGAGGGA AGGAAATTCA CCAGCGCAGC GACGAGGAAG GGGAACTCAG GACCCCTTCA AGTACACACT 003120
003121 GAGGTGTGAT CAGAGTTTTA TGGGCACTTT ATATGCTGTA ATCATAACGA TGTGTGTGCC TTGATATGCA CGCATATTCA 003200
003201 CGCATCAAAC GTGCATACAC ACACAGAGTG AATGTGCGCA TCCAATGTCA TGTGGGTGAA ATACAAGCAT CATACCCAGC 003280
003281 CCTACGAAAA AAAAATTCAC CCTGTCGGAC CAGGCTGGTG ACATACTTCG CTGGCGCATC TCCTTACTCA CTCTTACTTT 003360
003361 TCCGACCCCT CACCATTCCC TCTCCTGTGG CTTGGTAAAT ACACCTGCCC TCCGTGGAAG GTGAGTCCTG GACTGGCGTT 003440
003441 GCCAGGTTCG CATGTCCTCC CCAGAACCTC CGTCTGGCTC CAGGGACTCT CACTGAGCGG GTCTAGAGCA CCCAGCACTT 003520
003521 TTCAAGGAAC AGCCGCGGTT CCTTTGTCCC GCGGCTCCAG CCCCGTTCGG CCCAGCTCTC AGGGAAACGA AGCGCTCAGT 003600
003601 AAGAACTTTT GATATTAGTT TGTATGGGTA TTTACACTCT GGTGAGGGGA GCTGAGTACG GAAGTTCCAT TAATCATACT 003680
003681 CCAACCTTGG GTTTAGATAT TCAGTTTATG GGTTGGGAGA GGGAGTTTGC CGGAAAGAAA GCATCAAGGT TGGCCGCTGA 003760
003761 CTCCAGAGAA ATGAAAAGGG AGCAAGGTCG TTTTCTGTTT CTGGAAATCA AGAATTAGGA ATGGGCAACT ACAGGTGCTA 003840
003841 ACCAACAGAC CACTTTTTTG TTTTTTGGTA GCCCTTTGGC AGGGATAGTT TTTCCACCTT TGCCCGATAC AATTTAAAAA 003920
003921 AAAAAATCCT TTTATTATGG AATTTGTCAA ACACACACAC AAGCATAACA AACCCCTAGG TACCCATCTC CAAGTTTTGA 004000
004001 CCCCTATTAT AATTTCATCT TCAGTGTTTT ATTATCCACT TCCTCTCTCT CTATCTTTAG TATTTTAAAG TAAATCCCAG 004080
004081 ATAGCATCAC ATCATTTCAC CCCCACCATA GGATTTCAAA GATCTGTTAT ATTTCAAGAT TGAGTAAAAG GGCTTGAAAT 004160
004161 TGGGTTATTG CAATGAAACT CTAGAAAAAG CTTGAGGGTT CACCCAGGAG TAAGCTGGAC AAAAAAGGGG TTTGAGGGGT 004240
004241 GGACCCATCT TGCCTAAAAA TCTTGTCTCA TCTTTCTAAA AATTACATAT GAAAGAGGAA GATTTATGTT ACTTTTTTAT 004320
004321 ATGAGAGAAT CGTCCTTTAA TAGAAAATTT CTATTGCTGC ATCAGAATTA TGGAGGAACA CAAAAAACAT ACCTCAGTCC 004400
004401 TTAGTGTGTC CTAAATTAAC ACATATTCAC TTATTAGTGG GTAAATGACT ATATTTCATT TCAGCACAAC TTCTCCCCTG 004480
004481 GTAGAAACAC AAAAGAAATT TCTAATGATT AAACTAGGAA AGTTTGCACT GAATTGATGG CTTATCAGAG CAACCGCAGT 004560
004561 TTTCAGGAAG AAATTCAATG CCATGCGTTG AAAATATCCC CCTAGCAATA AGGGATTATT TTTAAAAAAG AATGAATAAA 004640
004641 GATGTTCTGG TTTCTTTTGT TTTAA

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Internal error

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[Xa2huywdqoVHp1h7D8rDGgAAAAI] 2019-10-21 12:17:01: Fatal exception of type "TypeError"

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