The Human GeneZFP161on 18p11.21–pter Encodes a Putativec-mycRepressor and Is Homologous to MurineZfp161(Chr 17) andZfp161-rs1(X Chr)

Sobek-Klocke, Ingeborg; Disqué-Kochem, Claudia; Ronsiek, Melanie; Klocke, Rainer; Jockusch, Harald; Breuning, Astrid; Ponstingl, Herwig; Rojas, Katherine; Overhauser, Joan; Eichenlaub-Ritter, Ursula

doi:10.1006/geno.1997.4784

Cited by 31 publications

(21 citation statements)

References 50 publications

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“…The human ZFP161 protein is highly homologous (98%) to ZF5, a putative murine repressor for MYC, with a growth-inhibitory function. 19 We anticipate that both ZFP161 and RBAK 20 are associated factors for 2 very functionally important proteins, MYC and RB, respectively, and may play important regulatory roles in cellular functions such as proliferation, differentiation, and apoptosis; to our knowledge, these genes have not been previously evaluated in hematopoiesis or leukemia. Another interesting protein is zinc finger protein 198 (ZNF 198).…”

Section: Discussionmentioning

confidence: 99%

Novel transcription factors in human CD34 antigen–positive hematopoietic cells

Gomes

Sharma

Edassery

et al. 2002

Blood

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Transcription factors (TFs) and the regulatory proteins that control them play key roles in hematopoiesis, controlling basic processes of cell growth and differentiation; disruption of these processes may lead to leukemogenesis. Here we attempt to identify functionally novel and partially characterized TFs/regulatory proteins that are expressed in undifferentiated hematopoietic tissue. We surveyed our database of 15 970 genes/expressed sequence tags (ESTs) representing the normal human CD34 ؉ cells transcriptosome (http:// westsun.hema.uic.edu/cd34.html), using the UniGene annotation text descriptor, to identify genes with motifs consistent with transcriptional regulators; 285 genes were identified. We also extracted the human homologues of the TFs reported in the murine stem cell database (SCdb; http://stemcell.princeton.edu/), selecting an additional 45 genes/ESTs. An exhaustive literature search of each of these 330 unique genes was performed to determine if any had been previously reported and to obtain additional characterizing information. Of the resulting gene list, 106 were considered to be potential TFs. Overall, the transcriptional regulator dataset consists of 165 novel or poorly characterized genes, including 25 that appeared to be TFs. Among these novel and poorly characterized genes are a cell growth regulatory with ring finger domain protein (CGR19, Hs.59106), an RB-associated CRAB repressor (RBAK, Hs.7222), a deathassociated transcription factor 1 (DATF1, Hs.155313), and a p38-interacting protein (P38IP, Hs. 171185). The identification of these novel and partially characterized potential transcriptional regulators adds a wealth of information to understanding the molecular aspects of hematopoiesis and hematopoietic disorders. (Blood.

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Section: Discussionmentioning

confidence: 99%

Novel transcription factors in human CD34 antigen–positive hematopoietic cells

Gomes

Sharma

Edassery

et al. 2002

Blood

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“…Conversely, we reasoned that motif depletion is a signature of a repressor because it suggests that motif absence is a condition for enhancer activity: GFI1 showed motif depletion in K562 enhancers and is indeed a known hematopoietic repressor (Hock and Orkin 2006); ZFP161, another known repressor (Sobek-Klocke et al 1997;Orlov et al 2007), showed motif depletion in HepG2 enhancers.…”

Section: Study Design and Enhancer Selectionmentioning

confidence: 99%

Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay

et al. 2013

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Genome-wide chromatin annotations have permitted the mapping of putative regulatory elements across multiple human cell types. However, their experimental dissection by directed regulatory motif disruption has remained unfeasible at the genome scale. Here, we use a massively parallel reporter assay (MPRA) to measure the transcriptional levels induced by 145-bp DNA segments centered on evolutionarily conserved regulatory motif instances within enhancer chromatin states. We select five predicted activators (HNF1, HNF4, FOXA, GATA, NFE2L2) and two predicted repressors (GFI1, ZFP161) and measure reporter expression in erythroleukemia (K562) and liver carcinoma (HepG2) cell lines. We test 2104 wild-type sequences and 3314 engineered enhancer variants containing targeted motif disruptions, each using 10 barcode tags and two replicates. The resulting data strongly confirm the enhancer activity and cell-type specificity of enhancer chromatin states, the ability of 145-bp segments to recapitulate both, the necessary role of regulatory motifs in enhancer function, and the complementary roles of activator and repressor motifs. We find statistically robust evidence that (1) disrupting the predicted activator motifs abolishes enhancer function, while silent or motif-improving changes maintain enhancer activity; (2) evolutionary conservation, nucleosome exclusion, binding of other factors, and strength of the motif match are predictive of enhancer activity; (3) scrambling repressor motifs leads to aberrant reporter expression in cell lines where the enhancers are usually inactive. Our results suggest a general strategy for deciphering cis-regulatory elements by systematic large-scale manipulation and provide quantitative enhancer activity measurements across thousands of constructs that can be mined to develop predictive models of gene expression.

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“…While for some genes the function and/or associated abnormal phenotypes are known, little is known in other cases. The gene ZF161 (zinc finger protein 161) has been proposed as a candidate gene for holoprosencephaly type 4 (MIM 142946 27 ). DYT7 has been postulated to be involved in idiopathic torsion dystonia.…”

Section: Alopecia In Cases With Chromosomal Abnormalities Affecting 18pmentioning

confidence: 99%

An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32–p11.23 in an Italian family

et al. 2000

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We report on a three-generation Italian family with dominant transmission of a form of hereditary hypotrichosis simplex (HHS). The nine affected adults presented with sparse, thin and short hair. Somewhat less sparse and longer hair was observed in the two affected young children in the third generation. Reduced hair growth affected the scalp and body, although normal eyelashes, eyebrows and growth of men's beards were observed. No associated abnormality was detected and the overall psychomotor development of the affected individuals was normal. A phenotypic variation was observed amongst the family members and is suggestive of a reduced penetrance of the trait or the effect of a modifying factor. After exclusion, in our family, of linkage to loci previously described in other forms of atrichia or hypotrichosis, we performed a genome-wide linkage analysis, which resulted in a positive lod score at 18p11.32-p11.23. We defined a critical region of about 35 cM flanked by markers D18S853 and D18S40. The highest two-point lod score was obtained with the microsatellite markers D18S1376, D18S53 and D18S453 (lod score of 3.31 at θ = 0.00). The 18p11.32-p11.23 locus represents the first chromosome region shown to be associated with hereditary hypotrichosis simplex.

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The Human GeneZFP161on 18p11.21–pter Encodes a Putativec-mycRepressor and Is Homologous to MurineZfp161(Chr 17) andZfp161-rs1(X Chr)

Cited by 31 publications

References 50 publications

Novel transcription factors in human CD34 antigen–positive hematopoietic cells

Novel transcription factors in human CD34 antigen–positive hematopoietic cells

Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay

An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32–p11.23 in an Italian family

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