Model for the fetal recruitment of simian γ‐globin genes based on findings from two new world monkeys Cebus apella and Callithrix jacchus (Platyrrhini, Primates)

• Autor(a) principal: Chiu, Ching-Hua
• Data de Publicação: 1999
• Outros Autores: Gregoire, L, Gumucho, Deborah L, Muniz, José Augusto Pereira Carneiro, Lancaster, W. D, Goodman, M
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• Texto Completo: https://patua.iec.gov.br/handle/iec/3787
• topic: Primatas / anatomia & histologia; Platirrinos / genética; Callithrix / genética; Cebus / genética; Dados de Sequência Molecular; Globinas / genética; gama-Globinas / classificação; gama-Globinas / genética; RNA Mensageiro / metabolismo; Reação em Cadeia da Polimerase / métodos

The originally embryonic γ‐globin locus duplicated and acquired a novel (fetal) pattern of expression in a defined time period (55–40 million years ago) during primate phylogeny. The objective of this study was to determine some of the factors that led to first the emergence of fetal γ specificity and then the maintenance of different fetal γ expression patterns in extant simian primates (e.g., human, capuchin monkey). Analyses focused on two platyrrhine (New World monkey) species: the common marmoset (Callithrix jacchus) and the brown capuchin monkey (Cebus apella), each of which has paired, non‐allelic γ loci (5′‐γ1–γ2‐3′). Quantitation of β‐type globin mRNAs expressed in a 4.5 week old embryo of Callithrix jacchus revealed that in addition to its primary ϵ‐globin message, considerable amounts of γ1 message and just trace levels of γ2 message are present. In contrast, analyses of γ‐globin messenger RNAs expressed in a Cebus apella fetal liver indicated that γ2 expression is at least 120 times greater than γ1 expression. Using a luciferase reporter and a transient assay system, the strengths of γ1 and γ2 promoter fragments of Cebus apella were compared in erythroid (K562) and non‐erythroid (HeLa) cell lines. Due to the lack of chromatin repression in a transient expression system, the results do not fully recapitulate globin expression. However, the results suggest that sequences contained within the Cebus γ1 and γ2 proximal promoter regions (−200 to +1 bp) can direct γ transcription in both cell lines. In K562 and, to a lesser extent, in HeLa cells Cebus γ2 promoter fragments were significantly stronger (P < 0.01) than γ1 promoter fragments. This is consistent with the fact that the Cebus γ1 promoter contains several mutations, including a proximal CCAAT box mutation (CCAAT→CCAAc). The ϵγ‐1 intergenic distances in these platyrrhines (5.4 kb in Cebus apella and 6.9 kb in Callithrix jacchus) are short, supporting the inference that it was also short in the stem simian primates. The results suggest that immediately following the γ duplication, the γ1 gene of the stem simians was still embryonic and the downstream γ2 gene was largely silent. A further inference is that once γ2 accumulated regulatory mutations that disrupted binding of fetal repressors, γ2 was expressed fetally and, through gene conversion, passed these characteristics to the γ1 gene. The fetal expression of γ1 is most evident in catarrhines (Old World monkeys and hominoids), which preferentially express the γ1 locus during fetal life.