hypermethylated in cancer 1 protein; Hic-1; zinc finger & BTB domain-containing protein 29 (HIC1, ZBTB29)

^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]^[12]^[13]

Function

transcriptional repressor
- recognizes & binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3'
tumor suppressor
development of head, face, limbs, ventral body wall
interacts with CtBP
role in down-regulation of SIRT1 thus role in regulation of p53/TP53-dependent apoptotic DNA-damage responses
specific target gene promoter association seems to be depend on corepressors, such as CTBP1 or CTBP2 & MTA1
regulation of SIRT1 transcription in response to nutrient deprivation seems to involve CTBP1
in cooperation with MTA1 represses transcription from CCND1/cyclin-D1 & CDKN1C/p57Kip2 in quiescent cells
role in regulation of the Wnt signaling pathway probably by association with TCF7L2 & preventing TCF7L2 & CTNNB1 association with promoters of TCF-responsive genes
seems to repress transcription from E2F1 & ATOH1 which involves ARID1A
probably represses transcription from ACKR3, FGFBP1 & EFNA1
acetylated on several residues, including Lys-333
- Lys-333 is deacetylated by SIRT1
sumoylated on Lys-333 by a PIAS family member, which enhances interaction with MTA1, positively regulates transcriptional repression activity & is enhanced by HDAC4
interacts with HIC2
interacts with CTBP1 & CTBP2
interacts with TCF7L2 & ARID1A
interacts with MTA1 & MBD3; indicative for an association with the NuRD complex

self-associates
the BTB domain inhibits the binding to a single consensus binding site, but mediates cooperative binding to multiple binding sites
belongs to the krueppel C2H2-type Zn+2-finger protein family, Hic subfamily
contains 1 BTB/POZ domain
contains 5 C2H2-type Zn+2 fingers

ubiquitously expressed, highest levels in lung, colon, prostate, thymus, testis, ovary

expression is absent or decreased in many tumor cells
- epigenetically silenced or deleted
defects in HIC1 associated with Miller-Dieker syndrome